Ultrasound catheter

ABSTRACT

A first tubular body having a first longitudinal axis extending centrally through the tubular body includes at least one delivery port extending through a wall of the first tubular body. A second tubular body having a second longitudinal axis extends through the second tubular body, the first and second longitudinal axes being displaced from each other such that an asymmetrical longitudinally extending gap is formed between an outer surface of the second tubular body and an interior surface of the first tubular body. A temperature sensor forming a thermocouple extending longitudinally within the gap between the first tubular body and the second tubular body. An inner core is positioned within the second tubular body. The inner core includes least one ultrasound element.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.62/173,863, filed Jun. 10, 2015, the entirety of which is herebyincorporated by reference herein.

FIELD

The present disclosure relates generally to an ultrasonic catheter andmore specifically to an ultrasonic catheter configured to deliverultrasonic energy and a therapeutic compound to a treatment site.

BACKGROUND

Several medical applications use ultrasonic energy. For example, U.S.Pat. Nos. 4,821,740, 4,953,565 and 5,007,438 disclose the use ofultrasonic energy to enhance the effect of various therapeuticcompounds. An ultrasonic catheter can be used to deliver ultrasonicenergy and a therapeutic compound to a treatment site within a patient'sbody. Such an ultrasonic catheter typically includes an ultrasoundassembly configured to generate ultrasonic energy and a fluid deliverylumen for delivering the therapeutic compound to the treatment site.

As taught in U.S. Pat. No. 6,001,069, ultrasonic catheters can be usedto treat human blood vessels that have become partially or completelyoccluded by plaque, thrombi, emboli or other substances that reduce theblood carrying capacity of the vessel. To remove or reduce theocclusion, the ultrasonic catheter is used to deliver solutionscontaining therapeutic compounds directly to the occlusion site.Ultrasonic energy generated by the ultrasound assembly enhances theeffect of the therapeutic compounds. Such a device can be used in thetreatment of diseases such as peripheral arterial occlusion, deep veinthrombosis or acute ischemic stroke. In such applications, theultrasonic energy enhances treatment of the occlusion with therapeuticcompounds such as urokinase, tissue plasminogen activator (“tPA”),recombinant tissue plasminogen activator (“rtPA”) and the like. Furtherinformation on enhancing the effect of a therapeutic compound usingultrasonic energy is provided in U.S. Pat. Nos. 5,318,014, 5,362,309,5,474,531, 5,628,728, 6,001,069, 6,210,356 and 7,341,569.

Another use for ultrasonic catheters is in the treatment of pulmonaryembolisms. Pulmonary embolisms (“PE”) are caused when a large blood clotobstructs the major blood vessels leading from the heart to the lungs.The victim's heart can be suddenly overwhelmed, with the task of pushingblood past this obstruction. About 5% of PEs are classified as massiveand can result in rapid heart failure, shock and death without immediatetherapy. Such massive PEs have traditionally been treated by a largedose of clot-dissolving drug (i.e., a thrombolytic). However, suchtreatment can result in unintended bleeding and even fatalities. Up to40% of PEs are less critical obstructions, often called sub-massive PE.Current treatment protocols include treatment with anti-coagulantmedication. Such treatments do not remove the clot but simply preventthe clot from growing larger. Recent studies suggest that failure toremove these sub-massive clots may have long-term adverse consequencesincluding recurrent PE, chronic pulmonary hypertension and death.

SUMMARY

In some embodiments, disclosed is an ultrasound catheter that includes afirst tubular body having a first longitudinal axis extending centrallythrough the tubular body, the first tubular body including at least onedelivery port extending through a wall of the first tubular body. Insome embodiments, the ultrasound catheter includes a second tubular bodyhaving a second longitudinal axis extending centrally through the secondtubular body, the first and second longitudinal axes being displacedfrom each other such that an asymmetrical longitudinally extending gapis formed between an outer surface of the second tubular body and aninterior surface of the first tubular body. In some embodiments, theultrasound catheter includes a temperature sensor forming a thermocoupleextending longitudinally within the gap between the first tubular bodyand the second tubular body. In some embodiments, the disclosureincludes an inner core positioned within the second tubular body, theinner core comprising at least one ultrasound element. In certainembodiments, the temperature sensor comprises a flexible circuit. Incertain embodiments, the temperature sensor comprises a plurality offilament pairs wherein each of the filaments is insulated; and aplurality of thermocouples wherein each of the plurality ofthermocouples are formed between each of the plurality of filamentpairs.

In some embodiments, disclosed is a method of manufacturing a catheter.In some embodiments, the method includes inserting an inner tubular bodyinto an outer tubular body. In some embodiments, the method includesplacing a temperature sensor between the outer and inner tubular body,wherein the temperature sensor is adjacent to an outer surface of theinner tubular body such that the inner tubular body does not extendalong the same longitudinal axis a the outer tubular body. In certainembodiments, the temperature sensor comprises a flexible circuit. Incertain embodiments, the temperature sensor comprises a plurality offilament pairs wherein each of the filaments is insulated; and aplurality of thermocouples wherein each of the plurality ofthermocouples are formed between each of the plurality of filamentpairs.

In some embodiments, disclosed is an ultrasound catheter including anelongate inner tubular body. In some embodiments, the ultrasoundcatheter includes an elongate outer tubular wherein the elongate innertubular body is positioned within the elongate outer tubular body toform an asymmetrical gap between an outer surface of the inner tubularbody and an interior surface of the elongate outer tubular body to forma fluid delivery lumen. In some embodiments, the ultrasound catheterincludes a temperature sensor extending along the outer surface of theinner tubular body within the gap. In some embodiments, the ultrasoundcatheter includes an inner core positioned within the inner tubular bodyand comprising at least one ultrasound element. In certain embodiments,the temperature sensor comprises a flexible circuit. In certainembodiments, the temperature sensor comprises a plurality of filamentpairs wherein each of the filaments is insulated; and a plurality ofthermocouples wherein each of the plurality of thermocouples are formedbetween each of the plurality of filament pairs.

In some embodiments, disclosed is a method of manufacturing a catheterincluding inserting an inner tubular body into an outer tubular body. Insome embodiments, the method of manufacturing includes placing atemperature sensor between the outer and inner tubular body, wherein thetemperature sensor is adjacent to an outer surface of the inner tubularbody such that the inner tubular body does not extend along the samelongitudinal axis a the outer tubular body. In certain embodiments, thetemperature sensor comprises a flexible circuit. In certain embodiments,the temperature sensor comprises a plurality of filament pairs whereineach of the filaments is insulated; and a plurality of thermocoupleswherein each of the plurality of thermocouples are formed between eachof the plurality of filament pairs

In some embodiments, disclosed is an ultrasound catheter including anelongate inner tubular body. In some embodiments, the ultrasoundcatheter includes an elongate outer tubular wherein the elongate innertubular body is positioned within the elongate outer tubular body toform an asymmetrical gap between an outer surface of the inner tubularbody and an interior surface of the elongate outer tubular body to forma fluid delivery lumen. In some embodiments, the ultrasound catheterincludes a temperature sensor extending along the outer surface of theinner tubular body within the gap. In some embodiments, the ultrasoundcatheter includes an inner core positioned within the inner tubular bodyand comprising at least one ultrasound element.

In some embodiments, disclosed is a flexible circuit for a catheter. Insome embodiments, the flexible circuit includes a plurality of tracesformed on the flexible circuit separated by insulating material. In someembodiments, the plurality of traces includes at least two traces of afirst material connected to a single trace of second dissimilar materialat different points along a length of the flexible circuit. In someembodiments, a temperature sensor for a catheter comprises a pluralityof filament pairs wherein each of the filaments is insulated; and aplurality of thermocouples wherein each of the plurality ofthermocouples are formed between each of the plurality of filamentpairs.

For purposes of summarizing the invention and the advantages achievedover the prior art, certain objects and advantages of the invention havebeen described in this application. It is to be understood that notnecessarily all such objects or advantages may be achieved in accordancewith any particular embodiment of the invention. Thus, for example,those skilled in the art will recognize that the invention may beembodied or carried out in a manner that achieves or optimizes oneadvantage or group of advantages as taught herein without necessarilyachieving other objects or advantages as may be taught or suggestedherein.

All of these embodiments are intended to be within the scope of theinvention herein disclosed. These and other embodiments of the presentinvention will become readily apparent to those skilled in the art fromthe following detailed description of the embodiments having referenceto the attached figures, the invention not being limited to anyparticular embodiment(s) disclosed.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments of the vascular occlusion treatment system areillustrated in the accompanying drawings, which are for illustrativepurposes only. The drawings comprise the following figures, in, whichlike numerals indicate like parts.

FIG. 1A is a schematic illustration of an ultrasonic catheter configuredfor insertion into large vessels of the human body.

FIG. 1B is a cross-sectional view of the ultrasonic catheter of FIG. 1A.

FIG. 1C is an enlarged cross-sectional view of a hub portion of theultrasonic catheter of FIG. 1A.

FIG. 1D is a side view of the hub portion ultrasonic catheter of FIG.1A.

FIG. 1E is an exploded illustration the hub portion of the ultrasoniccatheter of FIG. 1A.

FIG. 1F is an enlarged cross-sectional side view of a modified hubportion of the ultrasonic catheter of FIG. 1A.

FIG. 1G is a side view of an embodiment of the hub portion of theultrasonic catheter configured for insertion into the human body.

FIG. 1H is a side view of the embodiment of the hub portion of theultrasonic catheter of FIG. 1G with attached fluid tubes configured forinsertion into the human body.

FIG. 1I is an enlarged cross-sectional view of the hub portion of theultrasonic catheter of FIG. 1H along section A-A.

FIG. 1J is an enlarged cross-sectional view of the hub portion of FIG.1H along section B-B.

FIG. 1K is a side view of the exterior tubular body of the hub portionof FIG. 1G.

FIG. 1L is a front view of another embodiment of the hub portion of theultrasonic catheter configured for insertion into the human body.

FIG. 1M is a cross-sectional view of the hub portion of the ultrasoniccatheter of FIG. 1L.

FIG. 1N is an enlarged cross-sectional view of the hub portion of theultrasonic catheter of FIG. 1L along section B-B.

FIG. 1O is an enlarged cross-sectional view of the hub portion of theultrasonic catheter of FIG. 1L along section C-C.

FIG. 2 is a cross-sectional view of the ultrasonic catheter taken alongline 2-2 of FIG. 1C or anywhere along the length of the exterior tubularbody of FIG. 1K.

FIG. 2A is a cross-sectional, view of another embodiment of theultrasonic catheter taken along line 2-2 of FIG. 1C or anywhere alongthe length of the exterior tubular body of FIG. 1K.

FIG. 2B is a top cross-sectional view of an embodiment of a flexiblecircuit (“flexcircuit”) that can be configured to form a thermocouple toserve as a temperature sensor in the ultrasonic catheter illustrated inFIGS. 1A-1O and FIGS. 2-2A.

FIG. 2C is a side cross-sectional view of the embodiment of theflexcircuit illustrated in FIG. 2B.

FIG. 2D is a side view of an embodiment of a temperature sensor composedof a plurality of insulated wires configured to form a plurality ofthermocouples.

FIG. 2E is a top view of an embodiment of the temperature sensor of FIG.2D.

FIG. 2F is an enlarged top view of a thermocouple junction of thetemperature sensor of FIG. 2D.

FIG. 2G is a side view of another embodiment of a temperature sensorcomposed of a plurality of insulated wires configured to form aplurality of thermocouples.

FIG. 2H is a top view of another embodiment of a temperature sensor ofFIG. 2G.

FIG. 2I is an enlarged top view of a thermocouple junction of thetemperature sensor of FIG. 2G.

FIG. 3 is a schematic illustration of an elongate inner core configuredto be positioned within the central lumen of the catheter illustrated inFIG. 2.

FIG. 4 is a cross-sectional view of the elongate inner core of FIG. 3taken along line 4-4.

FIG. 5 is a schematic wiring diagram illustrating an exemplary techniquefor electrically connecting five groups of ultrasound radiating membersto form an ultrasound assembly.

FIG. 6 is a schematic wiring diagram illustrating an exemplary techniquefor electrically connecting one of the groups of FIG. 5.

FIG. 7A is a schematic illustration of the ultrasound assembly of FIG. 5housed within the inner core of FIG. 4.

FIG. 7B is a cross-sectional view of the ultrasound assembly of FIG. 7Ataken along line 7B-7B.

FIG. 7C is a cross-sectional view of the ultrasound assembly of FIG. 7Ataken along line 7C-7C.

FIG. 7D is a side view of an ultrasound assembly center wire twistedinto a helical configuration.

FIG. 8 illustrates the energy delivery section of the inner core of FIG.4 positioned within the energy delivery section of the tubular body ofFIG. 2.

FIG. 9 illustrates a wiring diagram for connecting a plurality oftemperature sensors with a common wire.

FIG. 10 is a block diagram of a feedback control system for use with anultrasonic catheter.

FIG. 11A is a side view of a treatment site.

FIG. 11B is a side view of the distal end of an ultrasonic catheterpositioned at the treatment site of FIG. 11A.

FIG. 11C is a cross-sectional schematic view of the distal end of theultrasonic catheter of FIG. 11B positioned at the treatment site beforea treatment.

FIG. 11D is a cross-sectional schematic view of the distal end of theultrasonic catheter of FIG. 11C, wherein an inner core has been insertedinto the tubular body to perform a treatment.

FIG. 12A is a horizontal cross-section showing a top view of anotherembodiment of a flexcircuit, with protective second coverlay 310removed, that can be configured to form a thermocouple to serve as atemperature sensor in the ultrasonic catheter illustrated in FIGS. 1A-E.

FIG. 12B is a vertical cross-sectional view of the embodiment of theflexcircuit illustrated in FIG. 12A at a more proximal point.

FIG. 13 illustrates a schematic of a method of manufacturing a cathetercomprising a flexcircuit.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

As described above, it is desired to provide an ultrasonic catheter alsoreferred to herein as “ultrasound catheter(s)” having various featuresand advantages. Examples of such features and advantages include theability to apply ultrasonic energy to a treatment site. In otherembodiments, the catheter has the ability to deliver a therapeuticcompound to the treatment site. Embodiments of an ultrasonic catheterhaving certain of these features and advantages are described herein.Methods of using such an ultrasonic catheter are also described herein.

The ultrasonic catheters also referred to herein as “ultrasoundcatheter(s)” described herein can be used to enhance the therapeuticeffects of therapeutic compounds at a treatment site within a patient'sbody. As used herein, the term “therapeutic compound” refers broadly,without limitation, to a drug, medicament, dissolution compound, geneticmaterial, anti-cancer drug, or any other substance capable of effectingphysiological functions. Additionally, any mixture comprising any suchsubstances is encompassed within this definition of “therapeuticcompound”, as well as any substance falling within the ordinary meaningof these terms. The enhancement of the effects of therapeutic compoundsusing ultrasonic energy is described in U.S. Pat. Nos. 5,318,014,5,362,309, 5,474,531, 5,628,728, 6,001,069 and 6,210,356, the entiredisclosures of which are hereby incorporated by herein by reference.Specifically, for applications that treat human blood vessels that havebecome partially or completely occluded by plaque, thrombi, emboli orother substances that reduce the blood carrying capacity of a vessel,suitable therapeutic compounds include, but are not limited to, anaqueous solution containing Heparin, Uronkinase, Streptokinase, TPA andBB-10153 (manufactured by British Biotech, Oxford, UK).

Certain features and aspects of the ultrasonic catheters disclosedherein may also find utility in applications where the ultrasonic energyitself provides a therapeutic effect. Examples of such therapeuticeffects include preventing or reducing stenosis and/or restenosis;tissue ablation, abrasion or disruption; promoting temporary orpermanent physiological changes in intracellular or intercellularstructures; and rupturing micro-balloons or micro-bubbles fortherapeutic compound delivery. Further information about such methodscan be found in U.S. Pat. Nos. 5,261,291 and 5,431,663, the entiredisclosures of which are hereby incorporated by herein by reference.

The ultrasonic catheters described herein can, be configured forapplying ultrasonic energy over a substantial length of a body lumen,such as, for example, the larger vessels located in the leg. In otherembodiments, the catheter can be configured for treatment of pulmonaryembolisms, (“PE”), which can be caused when a large blood clot obstructsthe major blood vessels leading from the heart to the lungs. However, itshould be appreciated that certain features and aspects of the presentdisclosure may be applied to catheters configured to be inserted intoother vessels or cavities such as the small cerebral vessels, in solidtissues, in duct systems and in body cavities. Additional embodimentsthat may be combined with certain features and aspects of theembodiments described herein are described in U.S. Patent PublicationUS2004/0019318, entitled “Ultrasound Assembly For Use With A Catheter”and filed Nov. 7, 2002, the entire disclosure of which is herebyincorporated herein by reference.

FIG. 1A schematically illustrates an ultrasonic catheter 10 configuredfor use in the large vessels of a patient's anatomy. For example, theultrasonic catheter 10 illustrated in FIG. 1A can be used to treat longsegment peripheral arterial occlusions, such as those in the vascularsystem of the leg. In other examples, the ultrasonic catheter 10illustrated in FIG. 1A can be used for treatment of a pulmonary embolismas described, for example, in U.S. Patent Publication US2012/0289889(filed May 10, 2012), which is hereby incorporated by reference hereinin its entirety. As will be explained in detail below, in someembodiments, the catheter is configured to be introduced into thepatient's the major blood vessels leading from the heart to the lungs(e.g., the pulmonary artery). In one embodiment of use, femoral venousaccess may be used to place the catheter 10 into such vessels. In suchembodiments, the catheter 10 can be advanced through femoral accesssite, through the heart and into the pulmonary artery. The dimensions ofthe catheter 10 are adjusted based on the particular application forwhich the catheter 10 is to be used.

As illustrated in FIG. 1A, the ultrasonic catheter 10 can include amulti-component, elongate flexible exterior tubular body 12 having aproximal region 14 and a distal region 15. The exterior tubular body 12can include a flexible energy delivery section 18 located in the distalregion 15 of the catheter 10. The exterior tubular body 12 and othercomponents of the catheter 10 can be manufactured in accordance with anyof a variety of techniques well known in the catheter manufacturingfield. Suitable materials and dimensions can be readily selected basedon the natural and anatomical dimensions of the treatment site and onthe desired percutaneous access site.

For example, in some embodiments, the proximal region 14 of the exteriortubular body 12 can comprise a material that has sufficient flexibility,kink resistance, rigidity and structural support to push the energydelivery section 18 through the patient's vasculature to a treatmentsite. Examples of such materials include, but are not limited to,extruded polytetrafluoroethylene (“PTFE”), polyethylenes (“PE”),polyamides and other similar materials. In certain embodiments, theproximal region 14 of the exterior tubular body 12 is reinforced bybraiding, mesh or other constructions to provide increased kinkresistance and pushability. For example, nickel titanium or stainlesssteel wires can be placed along or incorporated into the exteriortubular body 12 to reduce kinking.

In some embodiments configured for treating thrombus in the arteries ofthe leg, the exterior tubular body 12 has an outside diameter betweenabout 0.060 inches and about 0.075 inches (between about 0.15 cm andabout 0.19 cm). In another embodiment, the exterior tubular body 12 hasan outside diameter of about 0.071 inches (about 0.18 cm). In certainembodiments, the exterior tubular body 12 has an axial length ofapproximately 106 to 135 centimeters, although other lengths may byappropriate for other applications.

The energy delivery section 18 of the exterior tubular body 12 caninclude a material that is thinner than the material comprising theproximal region 14 of the exterior tubular body 12 or a material thathas a greater acoustic transparency. Thinner materials generally havegreater acoustic transparency than thicker materials. Suitable materialsfor the energy delivery section 18 can include, but are not limited to,high or low density polyethylenes, urethanes, nylons, and the like. Incertain modified embodiments, the energy delivery section 18 may beformed from the same material or a material of the same thickness as theproximal region 14.

In certain embodiments, the exterior tubular body 12 can be divided intothree sections of varying stiffness. In some embodiments, the firstsection, can include the proximal region 14, which can have a relativelyhigher stiffness. The second section, which can be located in anintermediate region between the proximal region 14 and the distal region15 of the exterior tubular body 12, can have a relatively lowerstiffness. This configuration further facilitates movement and placementof the catheter 10. The third section, which can include the energydelivery section 18, can, be generally lower in stiffness than thesecond section in spite of the presence of the ultrasound radiatingmembers 40.

To provide access to the interior of the exterior tubular body 12, aplurality of inlets can be fluidly connected to the proximal region 14of catheter 10. In some examples, the proximal region 14 of the catheter10 can include a cooling inlet port 46, a drug inlet port 32, and/or aproximal access port 31. In some embodiments, to provide an electricalconnection to the energy delivery section 18, the catheter 10 canfurther include a cable 45 that can include a connector 101 to thecontrol system 100 (shown in FIG. 10). In some variants, the cable 45can be connected to the catheter 10 at the proximal region 14 throughthe proximal access port 31. In some examples, the catheter 10 canfurther include a backend hub 33 that helps to secure the various inletports at the proximal region 14 of the catheter 10.

FIGS. 1B-E illustrate various views of the ultrasound catheter of FIG.1A. FIGS. 1B-1C illustrate cross-sectional views of the hub 33 and FIG.1D-D illustrates a side view of the hub 33. FIG. 1E illustrates anexploded view of the hub 33.

FIG. 2 illustrates a cross section of the exterior tubular body 12 takenalong line 2-2 in FIG. 1B. As shown in FIG. 2, in the illustratedembodiment the catheter 10 may be formed of two lumens—fluid deliverylumen 30 and central lumen 51, which can be formed from an interior wallof an exterior tubular body 12 and an interior wall of an interiortubular body 13, respectively. In some examples, the interior tubularbody 13 can be located within the exterior tubular body 12 such that agap 52 is formed between an interior wall of the exterior tubular body12 and an exterior wall of the interior tubular body 13 such that thefluid delivery lumen 30 extends coaxially about the interior tubularbody. In the embodiment shown in FIG. 2, the exterior tubular body 12has a first longitudinal axis L1 extending centrally through theexterior tubular body 12, and the interior tubular body 13 has a secondlongitudinal axis L2 extending centrally through the interior tubularbody 13. The first and second longitudinal axes L1, L2 are displacedfrom each other such that an asymmetrical gap 52 is formed between anouter surface of the interior tubular body 13 and an interior surface ofthe exterior tubular body 12. In other embodiments, more or fewer fluiddelivery lumens can be formed by a plurality of tubular bodies locatedwithin the exterior tubular body 12 and/or by the addition of dividersand/or channels.

With continued reference to FIG. 2, in some examples, the exteriortubular body 12 can further include a temperature sensor 20 that can bepositioned within the fluid delivery lumen 30 between the outsidesurface of the of the interior tubular body 13 and the interior surfaceof the exterior tubular body 12. As will be described in more detailbelow, the temperature sensor 20 shown in FIGS. 2 and 8 can be aflexible circuit or “flexcircuit” 220 as shown in FIGS. 2A and 2B orflexcircuit 320 as shown in FIGS. 12A and 12B. In some embodiments theflexible circuit is configured to form a thermocouple. In certainembodiments, the temperature sensor 20 shown in FIGS. 2 and 8 can be aribbon thermocouple 500 as shown in FIGS. 2D-2F or a ribbon thermocouple600 as shown in FIGS. 2G-2I. As described below, there are potentialadvantages to embodiments that utilize a flexible circuit 220, 320and/or thermocouple ribbon 500, 600 as described herein. However, incertain embodiments of the ultrasonic catheter 10, the temperaturesensor 20 can take other configurations or forms. In some embodiments,the temperature sensor 20 is positioned on a side of the interiortubular body 13 such that the interior tubular body 13 is positionedasymmetrically within the exterior tubular body 12. In such anarrangement, an asymmetrical longitudinally extending gap 52 is formedbetween an outer surface of the interior tubular body (corresponding tothe second tubular body) and an interior surface of the exterior tubularbody (corresponding to the first tubular body); thus in the illustratedarrangement the gap 52 between the outer surface of the interior tubularbody and the interior surface of the exterior tubular body can be anasymmetrical gap 52 (a crescent shape), which can have certainadvantages as described below. It is therefore preferred that theflexible circuit or ribbon thermocouple is positioned in the widestportion of the asymmetrical gap 52, and optionally, adjacent theexterior surface of the interior tubular body. In an embodiment, theflexible circuit or ribbon thermocouple can, be coupled to the outsidesurface of the interior tubular body 13 at one or more locations. In anembodiment, the flexible circuit or ribbon thermocouple can be coupledto the outside surface of the interior tubular body 13 at a distal endof the catheter 10. While not illustrated in FIGS. 2 and 8, in someembodiments, the flexible circuit or ribbon thermocouple can contact aninterior surface of the exterior tubular body 12 (corresponding to thefirst tubular body) in addition to or, as an alternative, in someembodiments, to contacting the outer surface of the interior tubularbody 13 (corresponding to the second tubular body). In certainembodiments, the flexible circuit 220 as shown in FIGS. 2A and 2B orflexcircuit 320 as shown in FIGS. 12A and 12B or be ribbon thermocouple500 as shown in FIGS. 2D-2F or a ribbon thermocouple 600 as shown inFIGS. 2G-2I when positioned as shown in FIGS. 2 and 8, can bend and becurved as shown in FIGS. 2 and 8 to form a crescent shape correspondingto the outer surface of the interior tubular body 13 (corresponding tothe second tubular body) and/or the interior surface of the exteriortubular body 12 (corresponding to the first tubular body).

FIG. 2A illustrates another embodiment of the cross section of anexterior tubular body 12. As shown in FIG. 2A, the exterior tubular body12 can be disposed about the interior tubular body 13. An inner core 706can be inserted within the interior tubular body 13 and positioned at atreatment site. As noted with regard to FIG. 2, the exterior tubularbody 12 can also include a temperature sensor 20 which can be arrangedin accordance with any of the embodiments described herein.

In some embodiments, the interior tubular body 13 can include an unevenexterior and/or interior surface that can, as will be discussed in moredetail, additional cooling within the device. In some embodiments, theinterior tubular body 13 can have a non-circular cross-section. In someembodiments, the interior tubular body 13 can include a plurality ofindentations 786 and/or protrusions 787 such that the interior tubularbody 13 does not have a circular interior surface and/or exteriorsurface. Because the diameter of the inner core 706 is less than thediameter of the interior tubular body, in an interior tubular body witha circular interior surface, the inner core 706 could be placed againstthe interior tubular body 13 such that there could be a relatively largeportion with no or minimal gap between the exterior surface of the innercore 706 and the interior surface of the interior tubular body 13 and/ora relatively large portion with no or minimal gap between the exteriorof the interior tubular body 13 and the interior of the exterior tubularbody 12. This can potentially cause uneven over-heating of the innercore 706. The indentations 786 can therefore ensure that cooling fluidwill have room to flow past the inner core 706 and contact more externalsurfaces of the inner core 706. In a similar manner, drug flowingbetween the interior tubular body 13 and the exterior tubular body 12can be more uniformly distributed between the two tubular components asa result of an uneven surface about the exterior of the interior tubularbody 13. In some embodiments, the exterior of the interior tubular body13 can include indentations 788 and/or protrusions 789. In someembodiments, the plurality of indentations 788 and/or protrusions 789can ensure that the inner core 706 does not cause overheating within theexterior tubular body 12. In some examples, as the indentations 786, 788and/or protrusions 787, 789 can be of any shape or size, this can reducemanufacturing costs as any imperfection on the inner and/or outersurface of the tubular body 13 would provide additional cooling benefitsto the inserted inner core 706. The indentations 786, 788 and/orprotrusions 787, 789 can extend longitudinally along the length of theinterior tubular body 13. In certain embodiments, the indentations 786,788 and/or protrusions 787, 789 can extend longitudinally along at least50% of the length of the interior tubular body 13 and along at least 75%of the length of the interior tubular body 13 and in certain embodimentsalong at least 90% of the length of the interior tubular body 13. Theembodiment of the interior tubular body 13 with indentations 786, 788and/or protrusions 787, 789 can be used in combination with thetemperature sensors described herein and/or used independently topromote uniform cooling. In some embodiments, the inner core includes athird longitudinal axis that is configured to extend centrally throughthe inner core. In some examples, the inner core is displaced from afirst longitudinal axis that is configured to extend centrally throughthe exterior tubular body. In some embodiments, the inner core isdisplaced from a second longitudinal axis that is configured to extendcentrally through the interior tubular body.

Temperature Sensor

Turning first to the flexcircuits illustrated in FIGS. 2B-C and 12A-12B,as described above, the temperature sensor 20 can comprise a flexiblecircuit (“flexcircuit”) that is configured to form one or morethermocouples. The flexcircuit can be used to measure the temperature atdifferent points along the length of the catheter 10, and so it ispreferred that the flexible circuit extends along the length of thecentral first tubular body.

FIG. 2B illustrates a top view of one embodiment of the flexcircuit 220and FIG. 2C is a cross-sectional view of the flexcircuit 220. FIGS.12A-12B illustrate two views of another embodiment of a flexcircuit 320.With reference to FIGS. 2B and 2C, on one embodiment, the flexcircuit220 is composed of a plurality of traces. In one embodiment, theflexcircuit 220 includes a first trace 207 that runs the entire lengthof the flexcircuit 220. The first trace is preferably constantan.Constantan is a copper-nickel alloy that has a constant resistivity overa wide range of temperatures. The first trace 207 can therefore providegood temperature sensitivity along its length. While a constantan traceis preferred, modified embodiments can include a trace of a differentmaterial.

To form the thermocouple, the flexcircuit 220 includes a plurality ofsecond traces formed of a material different than the first trace 207.Each individual trace of this plurality of second traces extends fromthe proximal end 230 to a different point along the length of theflexcircuit 220. In some examples, the individual traces of thisplurality of second traces are made of copper overlaid on theflexcircuit 220. In the illustrated embodiment, the first trace isConstantan and the plurality of second traces are formed from copper. Inother embodiments, the first and second materials can be a differentcombination of materials. For example, the first material can be Alumel(consisting of approximately 95% nickel, 2% manganese, 2% aluminium and1% silicon) and the second material can be Chromel (90% nickel and 10%chromium) as can be found in a Type K thermocouple or other combinationsof dissimilar materials. In one example, the flexcircuit 220 can includea trace 201 that extends from the proximal end 230 of the flexcircuit220 to a joint 211 at the distal end 240 of the flexcircuit 220.Similarly, the flexcircuit 220 can include one or more of any of thefollowing traces: trace 201 that extends from the proximal end 230 to ajoint 211 close to a distal end of the flexcircuit 220, trace 202 thatextends from the proximal end 230 to a joint 212, trace 203 that extendsfrom the proximal end 230 to a joint 213, trace 204 that extends fromthe proximal end 230 to a joint 214, trace 205 that, extends from theproximal end 230 to a joint 215, and trace 206 that extends from theproximal end 230 to a joint 216 closer to a proximal end of theflexcircuit 220. In some examples, the plurality of joints (e.g. joint211, joint 212, joint 213, joint 214, joint 215, and joint 216) allowsthe temperature to be taken along several points along the length of theflexcircuit 220. In some variants, this can help to measure thetemperature of the ultrasonic catheter along the entire length of thedevice or a portion of the device (e.g., a portion of the device thatincludes the ultrasound elements described below). In modifiedembodiments, the traces 201-206 and joints 211-216 can be arranged indifferent orders or configurations.

When temperature differential is experienced by the different conductors(e.g., between one of the traces 201-206 and the first trace 207), itproduces a voltage when the temperature of one of the spots differs fromthe reference temperature at other parts of the circuit. In this manner,temperatures along the flexcircuit 220 can be measured by measuring thevoltages between one of the traces 201-206 and the first trace 207. Theillustrated preferred embodiment of FIG. 2B includes a single firsttrace of Constantan and six (6) traces of copper, although in otherembodiments other dissimilar material combinations such as Alumel andChromel may be used together, respectively. In modified embodiments moreor fewer traces and/or traces formed of different materials eachdissimilar from the first trace may be used. An advantage of theillustrated embodiment is that a single first trace can be used tomeasure the temperature at multiple locations along the length of theflexcircuit 220, which can reduce the overall size of the flexcircuit ascompared to a circuit with multiple first traces; in the preferredembodiment, a single Constantan trace is used as the first trace, whichcan reduce the overall size of the flexcircuit as compared to a circuitwith multiple Constantan first traces. In modified embodiments, theflexcircuit can include multiple first traces that are each individuallyassociated with the individual traces of the plurality of second tracesof dissimilar materials.

In some embodiments, the flexcircuit 220 can be of variable length andcan be configured to run the entire length or a portion of the catheter10. Similarly, to measure temperature along the length of theflexcircuit 220, the distance between the joints 211-216 can be variedfor the catheter 10. In the one embodiment, the flexcircuit 220 can havea length l₁ from proximal end 230 to distal end 240 of about 115 cm. Insome embodiments, the distance between each of the joints 211-216 (e.g.length l₂, length l₃, length ₁₄, length l₅, length l₆) can beapproximately 10 cm. In additional embodiments, the distance betweeneach of the joints 211-216 can be between 1.0 cm and 50.0 cm dependingupon the number of joints and the desired overall length of theflexcircuit 220. The distance between the joints 211-216 need not beuniform in certain embodiments. As mentioned above, in one arrangement,the joints are positioned generally along the length of the catheter inwhich the ultrasound elements are positioned such that the temperatureof the catheter around the ultrasound elements can be monitored.Accordingly, in the illustrated embodiment the joints 211, 212, 213,214, 215, 216 are positioned in the energy delivery section 18 of theexterior tubular body 12.

FIG. 2C illustrates a side cross-sectional view of the flexcircuit 220.As described previously, the flexcircuit 220 can be formed by aplurality of layered traces. In one example, the flexcircuit 220includes the first trace 207 formed on a bottom middle layer 224. Insome variants, the first trace 207 can be 0.001 inch (0.003 cm) thick.The flexcircuit 220 can include three traces 202, 204, 206 and 201, 203,205 formed on a top middle layer 225, respectively, that can be formedfrom a different material than the first trace 207 and arranged asdescribed above. Each of the second or copper traces can be separatedfrom each other by adhesive 231 which can fill in the gaps betweenlayers of the flexcircuit and traces. In the illustrated embodiments theflexcircuit 220 can include a plurality of insulating layers betweeneach of the layers containing the traces. As discussed above, aside fromwhere a joint between two of the conductive layers are formed (e.g.joint 211, joint 212, joint 213, joint 214, joint 215, and joint 216),the plurality of insulating layers covers the length of the trace toinsulate each of the traces from each other. The flexible circuittherefore comprises a plurality of joints 211, 212, 213, 214, 215 and216 between the dissimilar materials of the first trace 207 and each ofthe plurality of second traces 201, 202, 203, 204, 205 and 206. Asillustrated in FIG. 12B, the flexcircuit 220 can include a bottomcoverlay 221, the bottom middle layer 224, top middle layer 225, and atop coverlay 227 that forms an insulating layer between each of thetrace layers. The flexcircuit 220 of the illustrated embodiment alsoincludes additional top insulating layer 218 and bottom insulating layer217 which can cover electrically conducting vias which form the joints211-216 that connect corresponding traces. In the preferred embodiment,each of these insulating layers can be formed of polyimide. In anembodiment, the top insulating layer 218 and bottom insulating layer 217can extend along the entire length of the flexcircuit 220. In anotherembodiment, the top insulating layer 218 and bottom insulating layer 217can cover portions of the flexcircuit 220 around the joints 211-216. Inone embodiment, the joints 211-216 are formed by forming an electricallyconducting via through the flexcircuit 220 to electrically connect therespective first trace 207 and second traces 201-206. The via can thenbe covered with the top insulating layer 218 and bottom insulating layer217. As shown in FIG. 2C, gaps between the respective layers and tracescan be filled in with an adhesive 231.

FIGS. 12A-12B illustrate another embodiment of a flexcircuit 320. FIG.12A shows a vertical cross-sectional view of the flexcircuit 320 at aproximal point. As shown, the flexcircuit 320 can include a plurality oftraces that are located on each of the top and bottom surfaces of theflexcircuit 320. As an example illustrated in FIG. 12B, the top surfacecan include a plurality of second traces 301, 302, and 303 whereas thebottom surface can include a plurality of second traces 304, 305, and306, with a first trace 307 running laterally on a side, in this casethe right side. The traces on the top and bottom surface of theflexcircuit 320 are separated by an insulator 308. In some examples, thebottom surface of the flexcircuit 320 can include a protective firstcoverlay 309 whereas the top surface of the flexcircuit 320 can includea protective second coverlay 310. The thickness of the flexcircuit 320can be approximately 0.004 cm and the width of the flexcircuit 320 canbe approximately 0.021 cm. In some embodiments, each of the traces ofthe flexcircuit 320 can be separated by a space of 0.003 cm.

The flexcircuit 320 can include a first material trace 307 that runsparallel to the length of the flexcircuit 320. In order to measuretemperature at a specific point along the flexcircuit 320, each of thetraces (e.g. trace 301, trace 302, trace 303, trace 304, trace 305, andtrace 306) runs a varied distance along the flexcircuit 320. Traces(e.g. trace 301, trace 302, trace 303, trace 304, trace 305, and trace306) can be made of a second material different from the first material.As with the embodiment of FIGS. 2A-2B, in one embodiment, the firstmaterial is Constantan and the second material is copper. In otherembodiments, other dissimilar material combinations such as Alumel andChromel can be used together. In some examples, where a temperaturemeasurement is desired, one of the traces can make a right angle andform a node to contact the constantan trace 307.

FIG. 12A is a horizontal cross section illustrating a top view of asection of the flexcircuit 320 with protective second coverlay 310removed. As illustrated, a temperature measurement can be obtained atnode 312—a point along the flexcircuit 320. Each of the traces (e.g.trace 301, trace 302, trace 303, trace 304, trace 305, and trace 306)can run parallel along the length of the flexcircuit 320. At varyingpoints, a node is formed where the trace turns to contact the firstmaterial trace 307. FIG. 12A shows a view taken at a more distal pointthan that shown in FIG. 12B, as at the segment of the flexcircuit 320shown in FIG. 12A, the trace 303 has already formed a node to determinethe temperature at a point further ahead proximally and therefore doesnot appear in this view. As well, trace 301 continues to run distallyacross the length of the segment shown in FIG. 12A and can thereforedetermine the temperature of the flexcircuit 320 distally further downalong the length of the flexcircuit 320. The node 312 (and any of nodes311, 313, 314, 315 and 316 (not shown)) can have a width of 0.011 cm anda height of 0.006 cm. Nodes 311, 312, 313, 314, 315 and 316 thereforeconstitute a plurality of joints between the dissimilar materials of thefirst material trace 307 and each of the plurality of second traces 301,302, 303, 304, 305 and 306.

In certain embodiments, the temperature sensor 20 can be a ribbonthermocouple composed of a plurality of wires or that are coupledtogether. For example, FIGS. 2D-2F illustrate an embodiment of ribbonthermocouple 500. In some embodiments, the ribbon thermocouple 500 canbe composed of a plurality of filaments and a plurality of thermocouplejunctions. The plurality of filaments can be adhered together along theentire length of the ribbon thermocouple 500, from the proximal end 550to the distal end 560. As will be discussed in more detail below, eachof the plurality of filaments are adhered together except within 0.50inches of the formed thermocouple junction.

As shown in FIG. 2E, in some embodiments, the ribbon thermocouple 500can include filament 501, filament 502, filament 503, filament 504,filament 505, filament 506, filament 507, filament 508, filament 509,filament 510, filament 511, and filament 512. In some examples, each ofthe filaments is composed of a conductor 520 and an insulator 522. Insome embodiments, the conductor 520 of each of the filaments is composedof a material such as copper or constantan. In some embodiments, thematerial of the conductor 520 of each of the filaments alternates. Forexample, filament 501, filament 503, filament 505, filament 507,filament 509, and filament 511 is composed of copper and filament 502,filament 504, filament 506, filament 508, filament 510, and filament 512is composed of constantan. In some embodiments, the insulator 522 ofeach of the filaments is composed of polyesterimide.

In some examples, the ribbon thermocouple 500 can be configured to forma plurality of thermocouples along the length of the ribbon thermocouple500 from the proximal end 550 to the distal end 560. In someembodiments, each of the thermocouples can be formed by strippingadjacent filaments of insulation and soldering the exposed conductor 520together to form a thermocouple joint. As illustrated in FIGS. 2D-2E,thermocouple junction 530 can be formed by stripping filament 501 andfilament 502 and soldering them together, thermocouple junction 531 canbe formed by stripping filament 503 and filament 504 and soldering themtogether, thermocouple junction 532 can be formed by stripping filament505 and filament 506 and soldering them together, thermocouple junction533 can be formed by filament 507 and filament 508 and soldering themtogether, thermocouple junction 534 can be formed by filament 509 andfilament 510 and soldering them together, and thermocouple junction 535can be formed by filament 511 and filament 512 and soldering themtogether.

In some examples, the two filaments of the thermocouple junction areformed of different materials. In some embodiments, one of the twofilaments of the thermocouple junction is formed of copper and one ofthe two filaments of the thermocouple junction is formed of constantan.

As shown in FIG. 2E, in some embodiments, the filaments are terminatedat the formed thermocouple junction. FIG. 2F illustrates an enlargedview of the thermocouple junction 535 along section A-A of FIG. 2E. Asdiscussed above, the distal end 560 of the pair of filaments has astripped portion 570. In some embodiments, the stripped portion 570 ofthe pair of filaments is attached together with a solder 540. In someexamples, the attachment of the two filaments is done by laser welding.In some examples, the insulation of the pair of filaments is laserstripped. In, some embodiments, the solder is composed of about 95% toabout 99% tin. In some examples, the thermocouple junction 535 includesa joint insulation 580. In some embodiments, the joint insulation 580 iscomposed of a polymer.

FIGS. 2G-2I illustrate another embodiment of a ribbon thermocouple 600composed of a plurality of filaments and a plurality of thermocouplejunctions. The plurality of filaments can be adhered together along theentire length of the ribbon thermocouple 600, from the proximal end 650to the distal end 660. As will be discussed in more detail below, each,of the plurality of filaments can be adhered together along the entirelength of the ribbon thermocouple 600.

As shown in FIG. 2H, in some embodiments, the ribbon thermocouple 600can include filament 601, filament 602, filament 603, filament 604,filament 605, filament 606, filament 607, filament 608, filament 609,filament 610, filament 611, and filament 612. In some examples, each ofthe filaments is composed of a conductor 620 and an insulator 622. Insome embodiments, the conductor 620 of each of the filaments is composedof a material such, as copper or constantan. In some embodiments, theconductor 620 of each of the filaments alternates. For example, filament601, filament 603, filament 605, filament 607, filament 609, andfilament 611 is composed of copper and filament 602, filament 604,filament 606, filament 608, filament 610, and filament 612 is composedof constantan.

In some examples, the ribbon thermocouple 600 can be configured to forma plurality of thermocouples along the length of the temperature sensor600 from the proximal end 650 to the distal end 660. In someembodiments, each of the thermocouples can be formed by strippingadjacent filaments of insulation and soldering the exposed conductor 520together to form a thermocouple joint. As illustrated in FIGS. 2G-2I,thermocouple junction 630 can be formed by stripping filament 601 andfilament 602 and soldering them together, thermocouple junction 631 canbe formed by stripping filament 603 and filament 604 and soldering themtogether, thermocouple junction 632 can be formed by stripping filament605 and filament 606 and soldering them together, thermocouple junction633 can be formed by filament 607 and filament 608 and soldering themtogether, thermocouple junction 634 can be formed by filament 609 andfilament 610 and soldering them together, and thermocouple junction 635can be formed by filament 611 and filament 612 and soldering themtogether.

In some examples, the two filaments of the thermocouple junction areformed of different materials. In some embodiments, one of the twofilaments of the thermocouple junction is formed of copper and one ofthe two filaments of the thermocouple junction is formed of constantan.

As shown in FIG. 2H, each of the filaments extends from the proximal end650 to the distal end 660, with the thermocouple junctions formed on aportion of the filaments. FIG. 2I illustrates an enlarged view of thethermocouple junction 635 along section A-A of FIG. 2H. As discussedabove, a portion of the pair of filaments has a stripped portion 670 toform a window in the insulator 622 along the pair of filaments. In someexamples, the insulation of the pair of filaments is laser stripped. Insome embodiments, the stripped portion 670 of the pair of filaments isattached together with a solder 640. In some examples, the attachment ofthe two filaments is done by laser welding. In some embodiments, thesolder is composed of about 95% to about 99% tin. In some embodiments,the thermocouple junction 635 includes a joint insulation 680. In someexamples, the joint insulation 680 is composed of a polymer.

The illustrated embodiments of FIGS. 2-2I and 12A-12B have severaladvantages. For example, prior art ultrasound catheters have included aplurality of separate thermocouple wires extending along the length ofthe catheter in order to measure the temperature of the catheter atseveral locations along the energy delivery section of the catheter. Byreplacing the plurality of wires with a single flexible circuit orribbon thermocouple with a plurality of nodes along the length of theflexcircuit or ribbon thermocouple, the complexity and costs associatedwith assembling the catheter can, be reduced as only a single element(flex circuit or ribbon thermocouple) needs to be inserted between thecatheter elements. In addition, as shown in FIGS. 2-2A, exterior tubularbody 12 and the interior tubular body 13 can be configured into anasymmetrical arrangement so as to accommodate the flexcircuit or ribbonthermocouple. This asymmetrical arrangement can provide additional roomfor the flexcircuit or ribbon thermocouple and its plurality of tracesor wires. However, surprisingly the asymmetrical shape of theasymmetrical gap 52 between the exterior tubular body 12 and theinterior tubular body 13 does not adversely affect the delivery of drugthrough the catheter and to the treatment zone.

In some embodiments, the ribbon thermocouple design of FIGS. 2D-2I caninclude a gap between each of the pair of wires that are configured toform a thermocouple. In some examples, the distance between theconductors of each of the wires is closer together than the distancebetween each of the pair of wires that are configured to form athermocouple. In some embodiments, this can help with the forming of thethermocouples. The distance between each of the pair of wires can aid inthe removal of insulation material and the subsequent electricalconnection of the exposed, conductors. As discussed, above, in someembodiments, the formation of an electrical connection of the exposedconductors can be through welding, soldering, or other electricalcoupling method.

Ultrasound Catheters

Turning back to FIG. 1E, to provide access to the interior of thecatheter 10, the proximal region 14 can include a distal hub 65 that canprovide access to the asymmetrical gap 52 and a proximal hub 60 that canbe configured to provide access to the central lumen 51. With referenceto FIGS. 1B and 1E, a proximal end of the exterior tubular body 12 canextend through a nose cone 70 and can be coupled to the distal hub 65through by a barbed fitting on the distal hub 65. In this manner, thedistal hub 65 can provide access to asymmetrical gap 52 between thetubular body 12 and the internal tubular body 13 as shown in FIG. 2.Fluid lumen 30 includes a gap 52 between the exterior tubular body 12and the internal tubular body 13. With reference to FIGS. 1B and 2, thefluid lumen inlet port 32 and the cable port 47 are in communicationwith this asymmetrical gap 52. That is to say, the fluid lumen inletport 32 is a first fluid injection port in fluid communication with thegap 52. A cable 45 can extend through the cable port 47 and can becoupled the temperature sensor 20. The interior tubular body 13 canextend through the distal hub 65 and can be coupled to the proximal hub60 such that the interior of the proximal hub 60 is in communicationwith the central lumen 51. As shown in FIG. 1B, the interior fluid port46 is in communication with the interior of the proximal hub 60 suchthat fluid injected through the fluid port 46 will enter the centrallumen 51. Thus, interior fluid port 46 is a fluid injection port influid communication with the interior of the interior tubular body 13.As illustrated, the proximal hub 60 can, in turn, be connected to aproximal end of the internal tubular body 13 by a barbed fitting on theproximal hub. While in the illustrated embodiment, barb fittings areused to connect the exterior tubular body 12 and the internal tubularbody 13 to the distal hub 65 and proximal hub 60 respectively, inmodified embodiments, other connection configurations can be such assuch as flanged and threaded flared connections.

For example, FIG. 1F illustrates a cross-sectional view of anotherembodiment of the backend hub 33′ As discussed with regard to thebackend hub 33 in FIGS. 1B & 1E, the backend hub 33′ can include aplurality of components that can provide access to the interior of theexterior tubular body 12. In some embodiments, the backend hub 33′ canbe configured to retain a proximal hub 60′.

Unlike the hub described in FIGS. 1B & 1E which is composed of a distalhub 65 and a proximal hub 60, the proximal hub 60′ spans the entirelength of the backend hub 33′ and provides a fluid connection to theinterior of the catheter 10. The proximal end of the interior tubularbody 13 is secured to the inside surface of the backend hub 33′ througha threaded flared fitting 71′.

The proximal hub 60′ also includes a plurality of inlets to providefluid communication with the interior of the catheter 10. The proximalhub 60′ can have a proximal access port 31′. In some examples, theproximal hub 60′ can include a second barb inlet 75′ which can providefluid communication to the gap 52 and a third barb inlet 63′ that canprovide access to the central lumen 51. In the embodiment illustrated inFIG. 1F, the cable 45′ can be provided through, an opening in, theproximal hub 60′ As discussed above, the cable 45′ can provide anelectrical connection for the temperature sensor 20.

The proximal hub 60′ can be secured to the nosecone 70′ through aplurality of components. As illustrated in FIG. 1F, the distal end ofthe proximal hub 60′ includes a plurality of threads 66 a′ that issecured to the inside surface of a flared fitting 66′ The flared fitting66′ can further include a plurality of barbed connectors that protrudefrom the surface of the nose cone 70 to secure the proximal hub 60′ andflanged fitting 66′ to the inside of the nosecone 70′.

With continued reference to FIGS. 1B and 1E, the distal hub 65 caninclude a first barb inlet 69 can be coupled to a connector 73 throughwhich a cable 45 can extend. The temperature sensor 20 can be connectedto the cable with one or both components extending partially through thefirst barb inlet 69 and connector 73. The distal hub 65 can also includea second barb inlet 75 which can be connected to the inlet port 32 toprovide fluid communication to the gap 52. The proximal hub 60 caninclude a third barb inlet 63 and a proximal access port 31 thatprovides access to the central lumen 51. The third barb inlet 63 can beconnected to the interior fluid port 46. In a modified embodiment, oneor more of the first, second and third barb inlets 69, 75 and/or 63 canbe replaced with flanged and/or flared fittings.

As discussed above, a plurality of components may be attached to theinlets of the distal hub 65 and proximal hub 60 to be in fluidcommunication with the interior of the exterior tubular body 12. Asillustrated in FIGS. 1B-1E, a cable 45 can be attached to or extendthrough the first barb inlet 69 to form an electrical connection withthe temperature sensor 20. In some embodiments the cable 45 is securedto the first barb inlet 69 through the use of connector 73 which caninclude an adhesive lining. In some embodiments, the cable 45 caninclude a connector 101 to the control system 100. Similarly, the fluidline 91 with fluid inlet port 32 can be attached to the second barbinlet 75 to provide fluid access to the asymmetrical gap 52. As well, insome embodiments, the cooling fluid line 92 with cooling fluid inletport 46 can be attached to the barb inlet 63 to provide fluid access tothe cooling fluid inlet port 46. The fluid inlet port 32 and coolingfluid inlet port 46 can be provided with luer fittings to facilitateconnections to other components.

In order to secure the aforementioned components in the proximal region14 of the catheter 10, the catheter 10 can include a housing structureto secure the fluid line 91 and cooling fluid line 92 to the inlets ofthe distal hub 65 and proximal hub 60. In some examples, as illustratedin FIG. 1E, the catheter 10 can include a backend hub 33 that has afirst and second portion. The two parts of the backend hub 33 can bedisposed about the proximal hub 60 and distal hub 65 so as to secure thedistal hub 65 and proximal hub 60 in place. In some examples, the 65 andproximal hub 60 is further secured by the nosecone 70. In someembodiments, the nosecone 70 can be further retained by the backend hub33 which secures the nosecone 70 at the distal end of the distal hub 65.

As noted above, in some embodiments, the arrangement of the exteriortubular body 12 and the interior tubular body 13 can be configured intoan asymmetrical arrangement so as to accommodate the temperature sensor20. As illustrated in FIG. 2, the central lumen 51 and temperaturesensor 20 are located within the fluid delivery lumen 30. Thecross-section of the exterior tubular body 12, as illustrated in FIG. 2,can be substantially constant along the length of the catheter 10. Thus,in such embodiments, substantially the same cross-section is present inboth the proximal region 14 and the distal region 15 of the catheter 10,including the energy delivery section 18. In certain embodiments, thesame or asymmetrically shaped cross-section is present along at least50% of the length of the catheter, in other embodiments, at least 75% ofthe length of the catheter and in other embodiments at least 90% of thelength of the catheter.

In some embodiments, the central lumen 51 has a minimum diameter greaterthan about 0.030 inches (greater than about 0.076 cm). In otherembodiments, the central lumen 51 has a minimum diameter greater thanabout 0.037 inches (greater than about 0.094 cm), although otherdimensions may be used in other applications. As described above, thecentral lumen 51 can extend through the length of the exterior tubularbody 12. As illustrated in FIG. 1C, the central lumen 51 can have adistal exit port 29 and a proximal access port 31. As noted above, insome embodiments, the proximal access port 31 forms part of the backendhub 33, which is attached to the proximal region 14 of the catheter 10.In some examples, the backend hub 33 can further include cooling fluidinlet port 46 which is hydraulically connected to the central lumen 51.In some embodiments, the backend hub 33 can also include a fluid inletport 32, which is in hydraulic connection with the asymmetrical gap 52in the fluid delivery lumen 30, and which can be hydraulically coupledto a source of drug or therapeutic compound via a hub such as a Luerfitting. This embodiment of the disclosure therefore comprises a firstfluid injection port (fluid inlet port 32) in fluid communication withthe gap 52.

The central lumen 51 can be configured to receive an inner core 34comprising a plurality of ultrasound radiating members extending along alength of the ultrasound catheter, FIG. 3 illustrates an embodiment ofelongate inner core 34, which can be inserted into the central lumen 51.In some embodiments, the elongate inner core 34 can include a proximalregion 36 and a distal region 38. A proximal hub 37 can be fitted on theinner core 34 at one end of the proximal region 36. As will, bedescribed below, in, an arrangement, one or more ultrasound radiatingmembers can be positioned within an inner core 34 located within thedistal region 38. The ultrasound radiating members 40 can form anultrasound assembly 42, which will be described in detail below. In oneembodiment, when the inner core 34 can be positioned within the centrallumen such that the ultrasound assembly 42 is positioned generallywithin the energy delivery section 18 of the catheter 10. As notedabove, in one embodiment, the joints 212, 213, 214, 215, 216 of the flexcircuit can be positioned adjacent the ultrasound, assembly 42 and/orwithin the energy delivery section 18 of the catheter 10 and/or thethermocouple junctions of a the ribbon thermocouple can be positionedadjacent the ultrasound assembly 42 and/or within the energy deliverysection 18 of the catheter.

FIGS. 1G-1J illustrate another embodiment of a back end hub 745, whichcan be used in the embodiments describe herein. As with the otherembodiments, the hub 745 can be coupled to the, the exterior tubularbody 12, the interior tubular body 13, and a plurality of inlets. Insome examples, the ultrasonic catheter 700 can include a plurality ofinlets. For example, the ultrasonic catheter 700 can include a firstbarb inlet 740, a second barb inlet 750, and a proximal access port 755.

In some embodiments, the hub 745 of the ultrasonic catheter 700 can becomposed of a plurality of nested components that are sealed together.As illustrated in FIGS. 1G-1H, in some examples, the hub 745 can becomposed of a cap 710 and a manifold body 730. A cross-section of eachof the portions of the hub 745 is illustrated in greater detail in FIGS.1I-1J. In some examples, the components of the hub 745 can be composedof a high density poly ethylene (“HDEV”). In some embodiments, thecomponents of the hub 745 can be composed of a polycarbonate.

Turning first to FIG. 1J, illustrated is a cross-section along circleB-B of the cap 710 in FIG. 1H. In some embodiments, the cap 710 isdisposed about a distal end of the distal end 736 of the manifold body730. As shown, in some examples, the cap 710 has internal threads 312that are disposed about the internal surface of the cap 710. The capinternal threads 712 are configured to engage with the external threads734 disposed about the external surface of the distal end 736. As willbe discussed in more detail below, in some embodiments, the manifoldbody 730 and the cap 710 have an interior lumen that secures theexterior tubular body 12 and interior tubular body 13.

In some embodiments, the cap 710 can include an internal taper 714 thatreduces in diameter. As shown in FIG. 1J, the internal taper 714 canaccommodate a flared end 722 of the exterior tubular body 12. FIG. 1Killustrates a side view of an embodiment of the exterior tubular body12. As illustrated, the exterior tubular body 12 can include a distalend 726 and a proximal end 728. In some embodiments, the flared end 722of the exterior tubular body 12 can be located at the proximal end 728.In some examples, the distal end 736 of the manifold body 730 can, whensecured within the cap 710, be configured to engage with and secure theflared end 722 of the exterior tubular body 12. As the distal end 736 ofthe manifold body 730 is rotated within the cap 710, the distal end 736of the manifold body 730 can apply pressure to the flared end 722 toform a seal 724. As will be discussed in more detail below, the seal 724can allow fluid to be pumped into the exterior tubular body 12 andprevent fluid, from leaking out of the exterior tubular body 12.

In some examples, as shown in FIG. 1J, the exterior tubular body 12 canbe disposed about the interior tubular body 13. As discussed above, theinterior tubular body 13 can be configured to accommodate the inner core706. In some embodiments, as will be discussed in more detail below, theinterior tubular body 13 can provide for a coolant to flow through theinterior tubular body 13 to maintain the temperature of the inner core706. In some embodiments, as will be discussed in more detail below, theexterior surface of the interior tubular body 13 and the interiorsurface of the exterior tubular body 12 can provide for a drug ortherapeutic compound to flow through.

Turning next to FIG. 1I, illustrated is a cross-section along circle A-Aof the manifold body 730 of the hub 745. In some embodiments, theproximal end 738 of the manifold body 730 can be configured to engagewith and secure the interior tubular body 13. In some examples, theproximal end 738 of the manifold body 730 can include internal threads732 that are disposed along the inner surface of the manifold body 730.In some embodiments, the proximal end of the interior tubular body 13can be engaged with a threaded insert 790. The external threads 792 ofthe threaded insert 790 can be rotated to engage with the internalthreads 732 of the manifold body 730.

In some embodiments, the manifold body 730 can include an internal taper733 that reduces in diameter. As shown in FIG. 1I, the internal taper733 can accommodate a flared end 782 of the interior tubular body 13. Insome examples, the distal end of the threaded insert 790 can, whensecured within the manifold body 730, be configured to engage with andsecure the flared end 782 of the interior tubular body 13. As thethreaded insert 790 is secured within the proximal end 738 of themanifold body 730, the distal end of the threaded insert 790 can applypressure to the flared end 782 to form a seal 784. As will be discussedin more detail below, the seal 784 can prevent fluid from leaking out ofthe interior tubular body 13.

As noted above, the hub 745 can include a number of openings to allowaccess to the interior of the exterior tubular body 12 and the interiortubular body 13 as shown in FIGS. 2 and 2A. In some embodiments, the hub745 can include the first barb inlet 740. The first barb inlet 740 canbe located near the distal end 736 of the manifold body 730. In someembodiments, the first barb inlet 740 can be fluidly connected to theopening between the interior surface of the exterior tubular body 12 andthe exterior surface of the interior tubular body 13. This can be, forexample, the asymmetric gap 52 of FIG. 2. The first barb inlet 740 canbe fluidly connected to a drug inlet tube 760 and allow a drug or atherapeutic compound to flow from the drug inlet tube 760 and into theexterior tubular body 12 such that the drug or therapeutic compoundflows between the interior surface of the exterior tubular body 12 andthe exterior surface of the interior tubular body 13.

In some examples, as illustrated in FIGS. 1G-1H, the hub 745 can includethe second barb inlet 750. The second barb inlet 750 can be located nearthe proximal end 738 of the manifold body 730. In some embodiments, thesecond barb inlet 750 can be fluidly connected to the interior of theinterior tubular body 13. This can be, for example, through the centrallumen as illustrated in FIG. 2. The second barb inlet 750 can be fluidlyconnected to a coolant inlet tube 770 and allow a cooling fluid to flowthrough the interior tubular body 13. As noted above, in some examples,the cooling fluid can help to maintain the temperature of the insertedinner core.

In some embodiments, as illustrated in FIGS. 1G-1H, the hub 745 caninclude a proximal access port 755 that can provide access to theinterior of the interior tubular body 13. In some embodiments, theproximal access port 755 can be configured to allow an inner core (forexample the inner core 34 of FIG. 2 or the inner core 706 of FIG. 2A) tobe inserted into the ultrasonic catheter 700.

FIGS. 1L-1O illustrate another embodiment of hub 845 which can be usedwith any of the embodiments described herein. In some embodiments, theultrasonic catheter 800 can include a hub 845, an exterior tubular body12, an interior tubular body 13, and, a plurality of inlets. Forexample, the ultrasonic catheter 800 can include a first barb inlet 822,a second barb inlet 832, and a proximal access port 855.

In some embodiments, the hub 845 of the ultrasonic catheter 800 can becomposed of a plurality of nested components that are secured together.In some examples, the various components of the hub 845 can be composedof a polycarbonate. As will be discussed in more detail below, the hub845 can include an external overmold that provides an easy and secureway of attaching the various components of the hub 845. As illustratedin FIG. 1L-1M, in some examples, the hub 845 can be composed of amanifold cap 810, a distal manifold 820, a proximal manifold 830, and anovermold 860. A cross-section of each of the junctions between each ofthe components of the hub 845 is illustrated in greater detail in FIGS.1N-1O.

Turning first to FIG. 1O, illustrated is a cross-section along circleC-C of the manifold cap 810 in FIG. 1M. In some embodiments, themanifold cap 810 is disposed about a distal end 824 of the distalmanifold 820. As illustrated, in some examples, the manifold cap 810 ispress fit 868 about the distal end 824 of the distal end 824.

In some embodiments, the manifold cap 810 can include an internal taper812 that reduces in diameter. As shown in FIGS. 1M and 1O, the internaltaper 812 can accommodate a flared end 842 of the exterior tubular body12. In some examples, when the distal end 824 of the distal manifold 820is secured within the manifold cap 810, the distal manifold 820 can beconfigured to engage with and secure the flared end 842 of the exteriortubular body 12. In some embodiments, as the distal, end 824 of thedistal manifold 820 is inserted within the manifold cap 810, the distalend 824 of the distal manifold 820 can apply pressure to the flared end842 to form a seal 862. As will be discussed in more detail below, theseal 862 can allow fluid to be pumped into the exterior tubular body 12and prevent fluid from leaking out of the exterior tubular body 12.

In some examples, as shown in FIGS. 1M and 1O, the exterior tubular body12 can be disposed about the interior tubular body 13. As discussedabove, the interior tubular body 13 can be configured to accommodate aninner core. In some embodiments, as will be discussed in more detailbelow, the interior tubular body 13 can provide for a coolant to flowthrough the interior tubular body 13 to maintain the temperature of theinserted inner core. In some embodiments, as will be discussed in moredetail below, the exterior surface of the interior tubular body 13 andthe interior surface of the exterior tubular body 12 can provide for adrug or therapeutic compound to flow through.

Turning next to FIGS. 1M-1N, illustrated is a cross-section along circleB-B of the connection between the proximal manifold 830 and the distalmanifold 820 of the hub 845. In some embodiments, the proximal end 828of the distal manifold 820 can, be disposed about the distal end 834 ofthe proximal manifold 830. In some examples, the distal manifold 820 ispress fit 866 about the proximal manifold 830.

In some embodiments, the proximal end 828 of the distal manifold 820 canbe configured to engage with and secure the interior tubular body 13. Insome embodiments, the distal manifold 820 can include an internal taper823 that reduces in diameter. As shown in FIG. 1N, the internal taper823 can accommodate a flared end 852 of the interior tubular body 13. Insome examples, the distal end 834 of the proximal, manifold 830 can,when secured within the proximal end 828 of the distal manifold 820, beconfigured to engage with and secure the flared end 852 of the interiortubular body 13. In some embodiments, the distal end 834 of the proximalmanifold 830 can apply pressure to the flared end 852 to form a seal862. As will be discussed in more detail below, the seal 862 can preventfluid from leaking out of the interior tubular body 13.

As noted above, the hub 845 can include a number of openings to allowaccess to the interior of the exterior tubular body 12 and the interiortubular body 13 as shown in FIGS. 2 and 2A. In some embodiments, the hub845 can include the first barb inlet 822. The first barb inlet 822 canbe located on the distal manifold 820. In some embodiments, the firstbarb inlet 822 can be fluidly connected to the opening between theinterior surface of the exterior tubular body 12 and the exteriorsurface of the interior tubular body 13. This can be, for example, theasymmetric gap 52 of FIG. 2. In some embodiments, the drug inlet tube826 can be disposed about the first barb inlet 822. The first barb inlet822 can be fluidly connected to the drug inlet tube 826 and allow a drugor a therapeutic compound to flow from the drug inlet tube 826 and intothe exterior tubular body 12 such that the drug or therapeutic compoundflows between the interior surface of the exterior tubular body 12 andthe exterior surface of the interior tubular body 13.

In some examples, as illustrated in FIG. 1M, the hub 845 can include thesecond barb inlet 832. The second barb inlet 832 can be located on theproximal manifold 830. In some embodiments, the proximal manifold 830can be fluidly connected to the interior of the interior tubular body13. This can be, for example, through the central lumen as illustratedin FIG. 2. In some embodiments, the coolant inlet tube 836 can bedisposed about the second barb inlet 832. The second barb inlet 832 canbe fluidly connected to the coolant inlet tube 836 and allow a coolingfluid to flow through the interior tubular body 13. As noted above, insome examples, the cooling fluid can help to maintain the temperature ofthe inserted inner core.

In some embodiments, as illustrated in FIG. 1M, the hub 845 can includea proximal access port 855 that can provide access to the interiortubular body 13. In some examples, the proximal access port 855 can beconfigured to allow an, inner core (for example the inner core 34 ofFIG. 2 or the inner core 706 of FIG. 2A) to be inserted into theultrasonic catheter 800.

As discussed above, in some embodiments, the hub 845 can include anovermold 860. In some examples, the overmold 860 can be composed of aco-polyester. In some embodiments, the overmold 860 can be composed of apolyamide. The overmold 860 can be configured to seal and secure thevarious components of the hub 845.

Details and various embodiments of the inner core 34 and its operationof can be found in several patents and patent applications filed by EKOSCorporation of Bothell Wash. including U.S. Pat. No. 7,220,239 and U.S.Patent Publication No. 2008/0171965, which are hereby incorporated byreference in their entirety.

As shown in the cross-section illustrated in FIG. 4, which is takenalong lines 4-4 in FIG. 3, the inner core 34 can have a cylindricalshape, with an outer diameter that permits the inner core 34 to beinserted into the central lumen 51 of the interior tubular body 13 viathe proximal access port 31. Suitable outer diameters of the inner core34 include, but are not limited to, about 0.010 inches to about 0.100inches (about 0.025 cm to about 0.254 cm). In other embodiments, theouter diameter of the inner core 34 can be between about 0.020 inchesand about 0.080 inches (about 0.051 cm to about 0.20 cm). In otherembodiments, the inner core 34 can have an outer diameter of about 0.035inches (about 0.089 cm).

Still referring to FIG. 4, the inner core 34 can include a cylindricalouter body 35 that houses the ultrasound assembly 42. The ultrasoundassembly 42 can include wiring and ultrasound radiating members,described in greater detail in FIGS. 5 through 7D, such that theultrasound assembly 42 is capable of radiating ultrasonic energy fromthe energy delivery section 41 of the inner core 34. The ultrasoundassembly 42 can be electrically connected to the backend hub 33, wherethe inner core 34 can be connected to a control system 100 via cable andthrough a connector (not shown). In one arrangement, an electricallyinsulating potting material 43 fills the inner core 34, surrounding theultrasound assembly 42, thus preventing or limiting movement of theultrasound assembly 42 with respect to the outer body 35. In oneembodiment, the thickness of the outer body 35 is between about 0.0002inches and about 0.010 inches (between about 0.0005 cm and about 0.025cm). In another embodiment, the thickness of the outer body 35 isbetween about 0.0002 inches and about 0.005 inches (between about 0.0005cm and about 0.01 cm). In yet another embodiment, the thickness of theouter body 35 is about 0.0005 inches (about 0.001 cm).

In some embodiments, the ultrasound assembly 42 comprises a plurality ofultrasound radiating members 40 that are divided into one or moregroups. For example, FIGS. 5 and 6 are schematic wiring diagramsillustrating one technique for connecting five groups of ultrasoundradiating members 40 to form the ultrasound assembly 42. As illustratedin FIG. 5, the ultrasound assembly 42 can include five groups G1, G2,G3, G4, and G5 of ultrasound radiating members 40 that can beelectrically connected to each other. The five groups are alsoelectrically connected to the control system 100. In some embodiments,two, three, or four groups of ultrasound radiating member 40 may beelectrically connected to each other and the control system 100.

In some embodiments, the ultrasound assembly 42 comprises five or less(i.e., one, two, three, four, or five) ultrasound radiating members 40.The ultrasound radiating members 40 may be divided into one or moregroups as described above. The reduced or limited number of ultrasound,radiating members 40 can allow the ultrasound assembly 42 to be drivenat a higher power.

As used herein, the terms “ultrasonic energy”, “ultrasound” and“ultrasonic” are broad terms, having their ordinary meanings, andfurther refer to, without limitation, mechanical energy transferredthrough longitudinal pressure or compression waves. Ultrasonic energycan be emitted as continuous or pulsed waves, depending on therequirements of a particular application. Additionally, ultrasonicenergy can be emitted in waveforms having various shapes, such assinusoidal waves, triangle waves, square waves, or other wave forms.Ultrasonic energy includes sound waves. In certain embodiments, theultrasonic energy has a frequency between about 20 kHz and about 20 MHz.For example, in one embodiment, the waves have a frequency between about500 kHz and about 20 MHz. In another embodiment, the waves have afrequency between about 1 MHz and about 3 MHz. In yet anotherembodiment, the waves have a frequency of about 2 MHz. The averageacoustic power is between about 0.01 watts and 300 watts. In oneembodiment, the average acoustic power is about 16 watts.

As used herein, the term “ultrasound radiating member” refers to anyapparatus capable of producing ultrasonic energy. For example, in oneembodiment, an ultrasound radiating member comprises an ultrasonictransducer, which converts electrical energy into ultrasonic energy. Asuitable example of an ultrasonic transducer for generating ultrasonicenergy from electrical energy includes, but is not limited to,piezoelectric ceramic oscillators. Piezoelectric ceramics typicallycomprise a crystalline material, such as quartz, that changes shape whenan electrical current is applied to the material. This change in shape,made oscillatory by an oscillating driving signal, creates ultrasonicsound waves. In other embodiments, ultrasonic energy can be generated byan ultrasonic transducer that is remote from the ultrasound radiatingmember, and the ultrasonic energy can be transmitted, via, for example,vibration through a wire that is coupled to the ultrasound radiatingmember.

Still referring to FIG. 5, the control circuitry 100 can include, amongother things, a voltage source 102. The voltage source 102 can comprisea positive terminal 104 and a negative terminal 106. The negativeterminal 106 is connected to common wire 108, which connects the fivegroups G1-G5 of ultrasound radiating members 40 in series. The positiveterminal 104 can be connected to a plurality of lead wires 110, whicheach connect to one of the five groups G1-G5 of ultrasound radiatingmembers 40. Thus, under this configuration, each of the five groupsG1-G5, one of which is illustrated in FIG. 6, can be connected to thepositive terminal 104 via one of the lead wires 110, and to the negativeterminal 106 via the common wire 108. The control circuitry can beconfigured as part of the control system 100 and can include circuits,control routines, controllers etc. configured to vary one or more powerparameters used to drive ultrasound radiating members 40.

Referring now to FIG. 6, in one embodiment, each group G1-G5 cancomprise a plurality of ultrasound radiating members 40. Each of theultrasound radiating members 40 can be electrically connected to thecommon wire 108 and to the lead wire 110 via one of two positive contactwires 112. Thus, when wired as illustrated, a constant voltagedifference will be applied to each ultrasound radiating member 40 in thegroup. Although the group illustrated in FIG. 6 comprises twelveultrasound radiating members 40, one of ordinary skill in the art willrecognize that more or fewer ultrasound radiating members 40 can beincluded in the group. Likewise, more or fewer than five groups can beincluded within the ultrasound assembly 42 illustrated in FIG. 5.

FIG. 7A illustrates one technique for arranging the components of theultrasound assembly 42 (as schematically illustrated in FIG. 5) into theinner core 34 (as schematically illustrated in FIG. 4). FIG. 7Aillustrates a cross-sectional view of the ultrasound assembly 42 takenwithin group GI in FIG. 5, as indicated by the presence of four leadwires 110. For example, if a cross-sectional view of the ultrasoundassembly 42 was taken within group G4 in FIG. 5, only one lead wire 110would be present (that is, the one lead wire connecting group G5).

Referring still to FIG. 7A, the common wire 108 can include an elongate,flat piece of electrically conductive material in electrical contactwith a pair of ultrasound radiating members 40. Each of the ultrasoundradiating members 40 can also be in electrical contact with a positivecontact wire 312. Because the common wire 108 is connected to thenegative terminal 106, and the positive contact wire 312 is connected tothe positive terminal 104, a voltage difference can be created acrosseach ultrasound radiating member 40. In some embodiments, the lead wires110 can be separated from the other components of the ultrasoundassembly 42, thus preventing interference with the operation of theultrasound radiating members 40 as described above. For example, in someembodiments, the inner core 34 is filled with an insulating pottingmaterial 43, thus deterring unwanted electrical contact between thevarious components of the ultrasound assembly 42.

FIGS. 7B and 7C illustrate cross-sectional views of the inner core 34 ofFIG. 7A taken along lines 7B-7B and 7C-7C, respectively. As illustratedin FIG. 7B, the ultrasound radiating members 40 are mounted in pairsalong the common wire 108. The ultrasound radiating members 40 areconnected by positive contact wires 112, such that substantially thesame voltage is applied to each ultrasound radiating member 40. Asillustrated in FIG. 7C, the common wire 108 can include wide regions108W upon which the ultrasound radiating members 40 can be mounted, thusreducing the likelihood that the paired ultrasound radiating members 40will short together. In certain embodiments, outside the wide regions108W, the common wire 108 may have a more conventional, rounded wireshape.

In a modified embodiment, such as illustrated in FIG. 7D, the commonwire 108 can be twisted to form a helical shape before being fixedwithin the inner core 34. In such embodiments, the ultrasound radiatingmembers 40 are oriented in a plurality of radial directions, thusenhancing the radial uniformity of the resulting ultrasonic energyfield.

One of ordinary skill in the art will recognize that the wiringarrangement described above can be modified to allow each group G1, G2,G3, G4, G5 to be independently powered. Specifically, by providing aseparate power source within the control system 100 for each group, eachgroup can be individually turned on or off, or can be driven with an,individualized power. This provides the advantage of allowing thedelivery of ultrasonic energy to be “turned off” in regions of thetreatment site where treatment is complete, thus preventing deleteriousor unnecessary ultrasonic energy to be applied to the patient.

The embodiments described above, and illustrated in FIGS. 5 through 7,illustrate a plurality of ultrasound radiating members groupedspatially. That is, in such embodiments, all of the ultrasound radiatingmembers within a certain group are positioned adjacent to each other,such that when a single group is activated, ultrasonic energy isdelivered at a specific length of the ultrasound assembly. However, inmodified embodiments, the ultrasound radiating members of a certaingroup may be spaced apart from each other, such that the ultrasoundradiating members within a certain group are not positioned adjacent toeach other. In such embodiments, when a single group is activated,ultrasonic energy can be delivered from a larger, spaced apart portionof the energy delivery section. Such modified embodiments may beadvantageous in applications wherein it is desired to deliver a lessfocused, more diffuse ultrasonic energy field to the treatment site.

In some embodiments, the ultrasound radiating members 40 compriserectangular lead zirconate titanate (“PZT”) ultrasound transducers. Insome embodiments, the ultrasound transducer may have dimensions of about0.017 inches by about 0.010 inches by about 0.080 inches (about 0.043 cmby about 0.025 cm by about 0.20 cm). In other embodiments, otherconfiguration may be used. For example, disc-shaped ultrasound radiatingmembers 40 can be used in other embodiments. In an embodiment, thecommon wire 108 comprises copper, and is about 0.005 inches (about 0.01cm) thick, although other electrically conductive materials and otherdimensions can be used in other embodiments. Lead wires 110 can comprise36 gauge electrical conductors, while positive contact wires 112 can be42 gauge electrical conductors. However, one of ordinary skill in theart will recognize that other wire gauges can be used in otherembodiments.

As described above, suitable frequencies for the ultrasound radiatingmember 40 include, but are not limited to, from about 20 kHz to about 20MHz. In one embodiment, the frequency is between about 500 kHz and 20MHz, and in another embodiment 1 MHz and 3 MHz. In yet anotherembodiment, the ultrasound radiating members 40 are operated with, afrequency of about 2 MHz.

FIG. 8 illustrates the inner core 34 positioned within the exteriortubular body 12 along a cross-sectional line similar to 2-2 in FIG. 1C.Details of the ultrasound assembly 42, provided in FIG. 7A, are omittedfor clarity. As described above, the inner core 34 can be slid withinthe central lumen 51 of the interior tubular body 13, thereby allowingthe inner core 34 to be positioned within the energy delivery section18. For example, in an embodiment, the materials comprising the innercore energy delivery section 41, the tubular body energy deliverysection 18, and the potting material 43 all comprise materials havingsimilar acoustic impedance, thereby minimizing ultrasonic energy lossesacross material interfaces.

FIG. 8 further illustrates placement of fluid delivery ports 58 withinthe tubular body energy delivery section 18. As illustrated, holes orslits can be formed from the fluid delivery lumen 30 through theexterior tubular body 12, thereby permitting fluid flow from theasymmetrical gap 52 to the treatment site. Thus, a source of therapeuticcompound coupled to the inlet port 32 can provide a hydraulic pressurewhich drives the therapeutic compound through the asymmetric gap 52 inthe fluid delivery lumen 30 and out the fluid delivery ports 58. Thus,inlet port 32 is a first fluid injection port in, fluid communicationwith the asymmetric gap 52.

In some embodiments, as illustrated in FIG. 8, the fluid delivery lumen30 is not evenly spaced around the circumference of the exterior tubularbody 12. As discussed, in some embodiments, the exterior tubular body 12further accommodates the temperature sensor 20. As noted above, thetemperature sensor can be a flexcircuit such as the flexcircuit 220described above with respect to FIGS. 2A and 2B or flexcircuit 320described with respect to FIGS. 12A and 12B. In some embodiments, thetemperature sensor 20 can contact the interior tubular body 13 to biasthe interior tubular body 13 against the interior surface of theexterior tubular body 12 and/or to one side of the fluid delivery lumen30.

In some examples, the configuration of the interior tubular body 13 andtemperature sensor 20 can provide a manufacturing benefit as it allowsfor the construction of the catheter 10 by simply inserting the interiortubular body 13 and temperature sensor 20 into the exterior tubular body12. This can allow the gap 52 to form between the exterior surface ofthe interior tubular body 13 and the interior surface of the exteriortubular body 12. In some embodiments, the size, location, and geometryof the fluid delivery ports 58 can be selected to provide uniform fluidflow from the fluid delivery ports 58 to the treatment site. Forexample, in one embodiment, the fluid delivery ports 58 closer to theproximal region of the energy delivery section 18 have smaller diametersthan fluid delivery ports 58 closer to the distal region of the energydelivery section 18, thereby allowing uniform delivery of fluid acrossthe entire energy delivery section 18. The configuration of the interiortubular body 13 can also provide better kink resistance and canpotentially reduce the ultrasound attenuation. In some embodiments wherethe fluid delivery ports 58 have similar sizes along the length of theexterior tubular body 12, the fluid delivery ports 58 have a diameterbetween about 0.0005 inches to about 0.0050 inches (between about 0.001cm to about 0.013 cm). In another embodiment in which the size of thefluid delivery ports 58 changes along the length of the exterior tubularbody 12, the fluid delivery ports 58 have a diameter between about 0.001inches to about 0.005 inches (between about 0.002 to about 0.01 cm) inthe proximal region of the energy delivery section 18, and between about0.0020 inches to about 0.005 inches (between about 0.005 cm to 0.01about cm) in the distal region of the energy delivery section 18. Theincrease in size between, fluid delivery ports 58 depends on thematerial composition of the exterior tubular body 12, and on the gap 52.In some embodiments, the fluid delivery ports 58 can be created in theexterior tubular body 12 by punching, drilling, burning, or ablating(e.g. with a laser), or by any other suitable methods. The drug ortherapeutic compound flowing along the length of the exterior tubularbody 12 can be increased by increasing the density of the number offluid delivery ports 58 toward the distal region 15 of the exteriortubular body 12.

It should be appreciated that it may be desirable to provide non-uniformfluid flow from the fluid delivery ports 58 to the treatment site. Insuch embodiment, the size, location and geometry of the fluid deliveryports 58 can be selected to provide such non-uniform fluid flow.

Referring still to FIG. 8, placement of the inner core 34 within theexterior tubular body 12 further defines cooling fluid lumen 44. Thecooling fluid lumen 44 can be formed between outer surface 39 of theinner core 34 and the inner surface of the interior tubular body 13. Insome embodiments, a cooling fluid can be introduced through the proximalaccess port 31 such that the cooling fluid flow is produced throughcooling fluid lumen 44 and out the distal exit port 29 (see FIG. 1C).Thus, in some embodiments, the proximal access port 31 is a fluidinjection port in fluid communication with an interior of the interiortubular body 13. In the illustrated arrangement, a cooling fluid can beintroduced through the port 46 such that the cooling fluid flow isproduced through cooling fluid lumen 44 and out the distal exit port 29.The cooling fluid lumen 44 can be evenly spaced around the inner core 34so as to provide uniform cooling fluid flow over the inner core 34. Sucha configuration can be desirable to remove unwanted thermal energy atthe treatment site. As will be explained below, the flow rate of thecooling fluid and the power to the ultrasound assembly 42 can beadjusted to maintain the temperature of the inner core 34 in the energydelivery section 41 within a desired range.

In some embodiments, the inner core 34 can be rotated or moved withinthe interior tubular body 13. Specifically, movement of the inner core34 can be accomplished by maneuvering the proximal hub 37 while holdingthe backend hub 33 stationary. The inner core outer body 35 is at leastpartially constructed from a material that provides enough structuralsupport to permit movement of the inner core 34 within the interiortubular body 13 without kinking of the interior tubular body 13 withoutkinking of the interior tubular body 13. Additionally, the inner coreouter body 35 can include a material having the ability to transmittorque. Suitable materials for the outer body 35 can include, but arenot limited to, polymides, polyesters, polyurethanes, thermoplasticelastomers and braided polyimides.

In one embodiment, the fluid delivery lumen 30 and the cooling fluidlumen 44 are open at the distal end of the exterior tubular body 12,thereby allowing the drug or therapeutic compound and the cooling fluidto pass into the patients' vasculature at the distal exit port. Or, ifdesired, the fluid delivery lumen 30 can be selectively occluded at thedistal end of the exterior tubular body 12, thereby providing additionalhydraulic pressure to drive the therapeutic compound out of the fluiddelivery ports 58. In either configuration, the inner core 34 canprevented from passing through the distal exit port by providing theinner core 34 with a length that is less than the length of the tubularbody. In other embodiments, a protrusion is formed on the internal sideof the tubular body in the distal region 15, thereby preventing theinner core 34 from passing through the distal exit port.

In still other embodiments, the catheter 10 further includes anocclusion device (not shown) positioned at the distal exit port 29. Theocclusion device can have a reduced inner diameter that can accommodatea guidewire, but that is less than the inner diameter of the centrallumen 51. Thus the inner core 34 is prevented from extending through theocclusion device and out the distal exit port 29. For example, suitableinner diameters for the occlusion device include, but are not limitedto, about 0.005 inches to about 0.050 inches (about 0.01 cm to about0.13 cm). In other embodiments, the occlusion device has a closed end,thus preventing cooling fluid, from leaving the catheter 10, and insteadrecirculating to the proximal region 14 of the exterior tubular body 12.These and other cooling fluid flow configurations permit the powerprovided to the ultrasound assembly 42 to be increased in proportion tothe cooling fluid flow rate. Additionally, certain cooling fluid flowconfigurations can reduce exposure of the patient's body to coolingfluids.

In certain embodiments, as illustrated in FIG. 8, the exterior tubularbody 12 can include a temperature sensor 20, which can be locatedadjacent the interior tubular body 13. In such embodiments, the proximalregion 14 of the exterior tubular body 12 includes a temperature sensorlead which can be incorporated into cable 45 (illustrated in FIG. 1B).As discussed above, in some embodiments the temperature sensor 20 canhave a minimal profile such that it can be placed within the exteriortubular body 12 adjacent the interior tubular body 13. In someembodiments, to have a minimal profile, the temperature sensor 20 can bemade of a flexible circuit as described above. For example, thetemperature sensor 20 can be the flexcircuit 220 of FIGS. 2A and 2B orthe flexcircuit 320 of FIGS. 12A and 12B. In other embodiments,temperature sensor 20 can include, but is not limited to, temperaturesensing diodes, thermistors, thermocouples, resistance temperaturedetectors (“RTDs”) and fiber optic temperature sensors which usethermalchromic liquid crystals. In some embodiments, suitabletemperature sensor 20 geometries can include a strip that lies along thelength of the exterior tubular body 12. In other embodiments, suitabletemperature sensor 20 geometries can include, but are not limited to, apoint, a patch or a stripe. In some embodiments, to provide for easy ofassembly, the temperature sensor(s) 20 can be positioned within theexterior tubular body 12 (as illustrated), and/or within one or more ofthe cooling fluid lumen 44.

FIG. 9 illustrates one embodiment for electrically connecting aplurality of temperature sensor 20. In such embodiments, eachtemperature sensor 20 is coupled to a common wire 61 (e.g., a Constantantrace) and is associated with an individual return wire 62. Accordingly,n+1 wires can be used to independently sense the temperature at ndistinct temperature sensor 20. The temperature at a particulartemperature sensor 20 can be determined by closing a switch 64 tocomplete a circuit between that thermocouple's individual return wire 62and the common wire 61. In embodiments wherein the temperature sensor 20comprise thermocouples, the temperature can be calculated from thevoltage in the circuit using, for example, a sensing circuit 63, whichcan be located within the external control circuitry 100.

In other embodiments, each temperature sensor 20 is independently wired.In such embodiments, 2n wires run through the exterior tubular body 12to independently sense the temperature at n independent temperaturesensor 20.

FIG. 10 illustrates one embodiment of a feedback control system 68 thatcan be used with the catheter 10. The feedback control system 68 can beintegrated into a control system that is connected to the inner core 34via cable and/or the temperature sensor 20 via connector 100 (asillustrated in FIG. 1B). The feedback control system 68 allows thetemperature at each temperature sensor 20 to be monitored and allows theoutput power of the energy source to be adjusted accordingly. Aphysician can, if desired, override the closed or open loop system.

The feedback control system 68 can include an energy source 70, powercircuits 72 and a power calculation device 74 that is coupled to theultrasound radiating members 40. A temperature measurement device 76 cancoupled to the temperature sensor 20 in the exterior tubular body 12. Aprocessing unit 78 can be coupled to the power calculation device 74,the power circuits 72 and a user interface and display 80.

In operation, the temperature at each temperature sensor 20 can bedetermined by the temperature measurement device 76. The processing unit78 receives each determined temperature from the temperature measurementdevice 76. The determined temperature can then be displayed to the userat the user interface and display 80.

The processing unit 78 comprises logic for generating a temperaturecontrol signal. The temperature control signal can be proportional tothe difference between the measured temperature and a desiredtemperature. The desired temperature can be determined by the user (atset at the user interface and display 80) or can be preset within theprocessing unit 78.

The temperature control signal can be received by the power circuits 72.In some embodiments, the power circuits 72 can be configured to adjustthe power level, voltage, phase and/or current of the electrical energysupplied to the ultrasound radiating members 40 from the energy source70. For example, when the temperature control signal is above aparticular level, the power supplied to a particular group of ultrasoundradiating members 40 can be reduced in response to that temperaturecontrol signal. Similarly, when the temperature control signal is belowa particular level, the power supplied to a particular group ofultrasound radiating members 40 can be increased in response to thattemperature control signal. After each power adjustment, the processingunit 78 can be configured to monitor the temperature sensor 20 andproduces another temperature control signal which is received by thepower circuits 72.

The processing unit 78 can further include safety control logic. Thesafety control logic detects when the temperature at a temperaturesensor 20 has exceeded a safety threshold. The processing unit 78 canthen provide a temperature control signal which causes the powercircuits 72 to stop the delivery of energy from the energy source 70 tothat particular group of ultrasound radiating members 40.

Because, in certain embodiments, the ultrasound radiating members 40 aremobile relative to the temperature sensor 20, it can be unclear whichgroup of ultrasound radiating members 40 should have a power, voltage,phase and/or current level adjustment. Consequently, each group ofultrasound radiating member 40 can be identically adjusted in certainembodiments. In a modified embodiment, the power, voltage, phase, and/orcurrent supplied to each group of ultrasound radiating members 40 isadjusted in response to the temperature sensor 20 which indicates thehighest temperature. Making voltage, phase and/or current adjustments inresponse to the temperature sensed by the temperature sensor 20indicating the highest temperature can reduce overheating of thetreatment site.

The processing unit 78 can also receive a power signal from a powercalculation device 74. The power signal can be used to determine thepower being received by each group of ultrasound radiating members 40.The determined power can then be displayed to the user on the userinterface and display 80.

As described above, the feedback control system 68 can be configured tomaintain tissue adjacent to the energy delivery section 18 below adesired temperature. For example, it can, be generally desirable toprevent tissue at a treatment site from increasing more than 6° C. Asdescribed above, the ultrasound radiating members 40 can be electricallyconnected such that each group of ultrasound radiating members 40generates an independent output. In certain embodiments, the output fromthe power circuit maintains a selected energy for each group ofultrasound radiating members 40 for a selected length of time.

The processing unit 78 can comprise a digital or analog controller, suchas a computer with, software. When the processing unit 78 is a computerit can include a central processing unit (“CPU”) coupled through asystem bus. As is well known in the art, the user interface and display80 can comprise a mouse, a keyboard, a disk drive, a display monitor, anonvolatile memory system, or any another. In some embodiments, the buscan be coupled to a program memory and a data memory.

In lieu of the series of power adjustments described above, a profile ofthe power to be delivered to each group of ultrasound radiating members40 can be incorporated into the processing unit 78, such that a presetamount of ultrasonic energy to be delivered is pre-profiled. In suchembodiments, the power delivered to each, group of ultrasound radiatingmembers 40 can then be adjusted according to the preset profiles.

The ultrasound radiating members can be operated in a pulsed mode. Forexample, in one embodiment, the time average electrical power suppliedto the ultrasound radiating members can be between about 0.1 watts and 2watts and can be between about 0.5 watts and 1.5 watts. In otherembodiments, the time average electrical power supplied to theultrasound radiating members is between, about 0.001 watts and about 5watts and can be between about 0.05 watts and about 3 watts. In someembodiments, the time average electrical power can be approximately 0.6watts or 1.2 watts to a pair of ultrasound radiating members. In otherembodiments, the time average electrical power over treatment time canbe approximately 0.45 watts or 1.2 watts to a pair of ultrasoundradiating members.

The duty cycle can be between about 1% and 50%. In some embodiments, theduty cycle can be between about 5% and 25%. In certain embodiments, theduty ratio can be approximately 7.5% or 15%. In other embodiments, theduty cycle can be between about 0.01% and about 90% and can be betweenabout 0.1% and about 50%. In certain embodiments, the duty ratio can beapproximately 7.5%, 15% or a variation between 1% and 30%. In someembodiments, the pulse averaged power to a pair of ultrasound radiatingmembers can be between about 0.1 watts and 20 watts and can further bebetween approximately 5 watts and 20 watts. In certain embodiments, thepulse averaged power to a pair of ultrasound radiating members can beapproximately 8 watts and 16 watts. In some embodiments, the pulseaveraged electrical power to a pair of ultrasound radiating members canbe between about 0.01 watts and about 20 watts and can be betweenapproximately 0.1 watts and 20 watts. In other embodiments, the pulseaveraged electrical power to a pair of ultrasound radiating members isapproximately 4 watts, 8 watts, 16 watts, or a variation of 1 to 8watts. The amplitude during each pulse can be constant or varied.

As described above, the amplitude, pulse width, pulse repetitionfrequency, average acoustic pressure or any combination of theseparameters can be constant or varied during each pulse or over a set ofportions. In a non-linear application of acoustic parameters the aboveranges can change significantly. Accordingly, the overall time averageelectrical power over treatment time may stay the same but not real-timeaverage power.

In some embodiments, the pulse repetition rate can be between about 5 Hzand 150 Hz and can further be between about 10 Hz and 50 Hz. In someembodiments, the pulse repetition rate is approximately 30 Hz. In otherembodiments, the pulse repetition can be between about 1 Hz and about 2kHz and more can be between about 1 Hz and about 50 Hz. In certainembodiments, the pulse repetition rate can be approximately 30 Hz, or avariation of about 10 to about 40 Hz. The pulse duration can be betweenabout 1 millisecond and 50 milliseconds and can be between about 1millisecond and 25 milliseconds. In certain embodiments, the pulseduration can be approximately 2.5 milliseconds or 5 milliseconds. Inother embodiments, the pulse duration or width can be between about 0.5millisecond and about 50 milliseconds and can be between about 0.1millisecond and about 25 milliseconds. In certain embodiments, the pulseduration can be approximately 2.5 milliseconds, 5 or a variation of 1 to8 milliseconds. In certain embodiments, the average acoustic pressurecan be between about 0.1 to about 20 MPa or in another embodimentbetween about 0.5 or about 0.74 to about 1.7 MPa. In one particularembodiment, the transducers can be operated at an average power ofapproximately 0.6 watts, a duty cycle of approximately 7.5%, a pulserepetition rate of 30 Hz, a pulse average electrical power ofapproximately 8 watts and a pulse duration of approximately 2.5milliseconds. In one particular embodiment, the transducers can beoperated at an average power of approximately 0.45 watts, a duty cycleof approximately 7.5%, a pulse repetition rate of 30 Hz, a pulse averageelectrical power of approximately 6 watts and a pulse duration ofapproximately 2.5 milliseconds. The ultrasound radiating member usedwith the electrical parameters described herein can have an acousticefficiency greater than 50%. In some embodiments, the acousticefficiency can be greater than 75%. The ultrasound radiating member canbe formed a variety of shapes, such as, cylindrical (solid or hollow),flat, bar, triangular, and the like. The length of the ultrasoundradiating member can be between about 0.1 cm and about 0.5 cm. Thethickness or diameter of the ultrasound radiating members can be betweenabout 0.02 cm and about 0.2 cm.

FIGS. 11A through 11D illustrate a method for using the ultrasoniccatheter 10. As illustrated in FIG. 11A, a guidewire 84 similar to aguidewire used in typical angioplasty procedures can be directed througha patient's vessels 86 to a treatment site 88 which includes a clot 90.The guidewire 84 can be directed through the clot 90. Suitable vessels86 can include, but are not limited to, the large periphery bloodvessels of the body. Additionally, as mentioned above, the ultrasoniccatheter 10 also has utility in various imaging applications or inapplications for treating and/or diagnosing other diseases in other bodyparts.

As illustrated in FIG. 11B, the catheter 10 can be slid over andadvanced along the guidewire 84 using conventional over-the-guidewiretechniques with the guidewire extending through the interior tubularbody 13. The catheter 10 can be advanced until the energy deliverysection 18 of the exterior tubular body 12 is positioned at the clot 90.In certain embodiments, radiopaque markers (not shown) are positionedalong the energy delivery section 18 of the exterior tubular body 12 toaid in the positioning of the exterior tubular body 12 of the catheter10 within the treatment site 88.

As illustrated in FIG. 11C, the guidewire 84 can then be withdrawn fromthe catheter 10 by pulling the guidewire 84 from the proximal region 14of the catheter 10 while holding the catheter stationary. This leavescatheter 10 (exterior body 12 shown in FIG. 11C) positioned at thetreatment site 88.

As illustrated in FIG. 11D, the inner core 34 can then be inserted intointerior tubular body 13 until the ultrasound assembly 42 is positionedat least partially within the energy delivery section 18 of the exteriortubular body 12. Once the inner core 34 is properly positioned, theultrasound assembly 42 can be activated to deliver ultrasonic energythrough the energy delivery section 18 to the clot 90. As describedabove, suitable ultrasonic energy is delivered with a frequency betweenabout 20 kHz and about 20 MHz.

In a certain embodiment, the ultrasound assembly 42 comprises sixtyultrasound radiating members 40 spaced over a length of approximately 30to 50 cm. In such embodiments, the catheter 10 can be used to treat anelongate clot 90 without requiring movement of or repositioning of thecatheter 10 during the treatment. However, in some embodiments, theinner core 34 can be moved or rotated within the catheter 10 during thetreatment. Such movement can be accomplished by maneuvering the proximalhub 37 of the inner core 34 while holding the backend hub 33 stationary.

Referring again to FIG. 11D, arrows 48 indicate that a cooling fluidflows through the cooling fluid lumen 44 and out the distal exit port29. Likewise, arrows 49 indicated that a therapeutic compound flowsthrough gap 52 in the fluid delivery lumen 30 and out the fluid deliveryports 58 to the treatment site 88. In the schematic illustrations ofFIGS. 11A and 11D, the fluid delivery ports 58 are shown in a differentlocation than illustrated in FIG. 8.

The cooling fluid can be delivered before, after, during orintermittently with the delivery of ultrasonic energy. Similarly, thetherapeutic compound can be delivered before, after, during orintermittently with the delivery of ultrasonic energy. Consequently, thesteps illustrated in FIGS. 11A through 11D can be performed in a varietyof different orders than that described above. The therapeutic compoundand ultrasonic energy can be applied until the clot 90 is partially orentirely dissolved. Once the clot 90 has been dissolved to the desireddegree, the exterior tubular body 12 and the inner core 34 are withdrawnfrom the treatment site 88.

Pulmonary Embolism Treatment

In some embodiments, the ultrasonic catheter 10 can be configured to beintroduced into the major blood vessels leading from the heart to thelungs (e.g., the pulmonary artery). In one embodiment of use, femoralvenous access may be used to place the ultrasonic catheter 10 into suchvessels. In such embodiments, the ultrasonic catheter 10 can be advancedthrough femoral access site, through the heart and into the pulmonaryartery. The dimensions of the ultrasonic catheter 10 are adjusted basedon the particular application for which the ultrasonic catheter 10 is tobe used.

As noted above, the ultrasound catheter 10 can, also be used fortreating PE. The ultrasound catheter 10 can be introduced into apatient's pulmonary artery over a guidewire. The distal region 15 of theultrasound catheter 10 is then advanced to the treatment site within thepulmonary artery. The ultrasound energy delivery section 18 of theultrasound catheter can be positioned across the treatment site usingfluoroscopic guidance via radiopaque marker located near the proximalend and the distal end of the ultrasound energy delivery section 18.Once the ultrasound catheter 10 is successfully placed, the guidewiremay be removed from the ultrasound catheter 10. In the embodimentsdepicted in FIGS. 1-11, the elongate inner core 34 comprising at leastone ultrasound radiating member 40 can then be inserted into the centrallumen 51 of the ultrasound catheter 10. The at least one ultrasoundradiating member 40 can be positioned along the energy delivery section18 of the ultrasound catheter 10. In some embodiments, at least onecooling lumen 44 is formed between an outer surface 39 of the inner core34 and an inner surface of the interior tubular body 13. The coolantinfusion pump is attached to the cooling fluid inlet port 46, which isin communication with the at least one cooling fluid lumen 44. The druginfusion pump can then be connected to the fluid inlet port 32, which isin communication with the asymmetric gap 52 in the at least one fluiddelivery lumen 30.

The thrombolytic drug can then be delivered to the treatment sitethrough at least one fluid delivery lumen 30. In some embodiments, aplurality of fluid delivery ports 58 is in fluid communication with thefluid delivery lumen 30 can be located on, the ultrasound catheter atthe ultrasound energy delivery section 18. The drug can be infusedthrough the fluid delivery ports 58 to the treatment site.

The ultrasound energy may be delivered to the treatment sitesimultaneously or intermittently with the infusion of the thrombolyticdrug. In some embodiments, the ultrasound energy is emitted to thetreatment site prior to the thrombolytic drug being delivered. In someembodiments, the thrombolytic drug is delivered to the treatment siteprior to the ultrasound energy being emitted. The ultrasound energy maybe emitted according to the manner described above. In some embodiment,the power parameter and the physiological parameter of at least oneultrasound radiating member 40 may be varied as described above.

In some embodiments, the elongate, inner core 34 may comprise five orless (i.e., one, two, three, four, or five) ultrasound radiating members40. In some variants, by limiting the number of the ultrasound radiatingmembers 40, it is can be possible to drive the ultrasound radiatingmembers at a higher power for PE treatments.

High intensity ultrasound catheter may also be especially effective intreating pulmonary embolism. In some embodiments, the size of one ormore ultrasound radiating members 40 positioned in the elongate innercore 34 can be increased to generate high intensity ultrasound. In otherwords, larger ultrasound radiating members can be used for this purpose.In some embodiments, positioning the ultrasound radiating members lessthan 1 cm apart can result in higher intensity ultrasound output.

Without being bound to the theory, the ultrasound can prepare the clotby unwinding the fibrin strands and increasing the permeability of theclot. Acoustic pressure waves and micro-streaming force the delivereddrug into the clot, quickly permeating the clot with drug. As the drugis absorbed into the clot it binds with exposed plasminogen receptorsites. Once bound in the clot, the drug is no longer in freecirculation, does not pass through the liver and is not metabolized.

In some embodiments, recombinant tissue plasminogen activator (rt-PA orActilyse®) can be used with the ultrasound catheter 10 for the treatmentof pulmonary embolism. The effective infusion dosage may range fromabout 0.12 mg/hr to about 2 mg/hr, from about 0.2 mg/hr to about 1.5mg/hr, from about 0.5 mg/hr to about 1.5 mg/hr, or from about 1 mg/hr toabout 2 mg/hr. The rt-PA maximum total infusion dose may be from about10 mg to about 30 mg, from about 10 mg to about 20 mg, or about 25 mg.In some embodiment, as rt-PA is infused at a rate of about 1 mg/hr toabout 2 mg/hr for about 3 to about 5 hours, then the infusion rate isdecreased to about 0.5 mg/hr for 10 hours. In some embodiments, rt-PA isinfused at a rate of about 1 mg/hr to about 2 mg/hr for about 5 hours,and then the infusion rate is decreased to about 0.5 mg/hr for 10 hours.

Other potential drugs that may be used with the ultrasound catheter fortreating pulmonary embolism may include fibrinolytic compounds such asurokinase (Abbokinase®, Abbott laboratories, USA), streptokinase(Streptase®, Behringwerke AG), and reteplase (Retavase™, Centocor,Inc.). The enzymatic activity and stability of these fibrinolytics(including rt-PA) are not changed after exposure to therapeuticultrasound.

In general, digital angiographic equipment is used to aid theperformance of the ultrasound catheter treatment procedure. Continuousinvasive pressure monitoring and ECG-monitoring can be used forobtaining baseline hemodynamic parameters, including heart rate, rightatrial, right ventricular, and pulmonary artery pressures, as well asthe mixed-venous oxygen saturation from the pulmonary artery. A systemicarterial blood pressure and a systemic oxygen saturation can also bemeasured if an arterial line is in place. Otherwise, the systemic cuffblood pressure is measured and the oxygen saturation is obtained bypulse oximetry. In one embodiment, a blood pressure sensor is integratedinto the ultrasound catheter.

In some embodiments, a feedback control loop configured to monitor thebaseline hemodynamic parameters and/or mixed-venous oxygen saturationcan be integrated into the control system 100. The output power of theenergy source can then be adjusted according to the readings. Aphysician can override the closed or open loop system if so desired.

In some embodiments, an unilateral filling defect in one main orproximal lower lobe pulmonary artery by contrast-enhanced chest CTindicates that only one ultrasound catheter is to be placed into thepulmonary artery. In case of bilateral filling defect is detected inboth main or proximal lower lobe pulmonary arteries bycontrast-enhancing chest CT, two ultrasound catheters may be placed.

As noted above, in some embodiments, femoral venous access may be usedfor placing the ultrasound catheter in the pulmonary arteries. Forexample, a 6F introducer sheath is inserted in the common femoral vein.An exchange-length 0.035-inch (0.089-cm) angled guidewire, for examplethe Terumo□ soft wire, may be used for probing the embolic occlusionunder fluoroscopy. A 5F standard angiographic catheter, such as amultipurpose catheter or pigtail catheter or any other pulmonaryangiographic catheter may be used with small manual contrast injectionsfor localizing the embolic occlusion and for positioning the cathetersuch that the energy delivery section 18 of the ultrasound catheterspans the thrombus. If the distal extent of the embolus is not visibleangiographically or if it is difficult to probe the embolic occlusion, a4F Terumo glide catheter may be used for obtaining very small selectivecontrast injections beyond the presumed thrombotic occlusion aftertransiently removing the 0.035 wire. After the wire is successfullyplaced beyond the thrombotic occlusion in a lower lobe segmental branch,the angiographic catheter is exchanged for the ultrasound catheter.

Finally, in embodiments wherein the ultrasound catheter includingelongate inner core with ultrasound catheter (as shown in FIGS. 1-11) isused, the 0.035-inch (0.089-cm) guidewire can be removed and theelongate inner core with ultrasound radiating member(s) 40 is insertedinto the ultrasound catheter. The therapeutic compound can be introducedthrough the at least one fluid delivery lumen 30 and out of the fluiddelivery port(s) 58 to the treatment site.

After about 12 to about 15 hours of drug infusion, the rt-PA infusioncan be replaced with heparinized saline infusion (about 1 μg/ml) at aninfusion rate of 5 ml/hr. Sometime between about 16 and about 24 hoursafter the start of the rt-PA infusion, follow-up hemodynamicmeasurements (heart rate, systemic arterial pressure, right atrial,right ventricular and pulmonary artery pressures, mixed venous and pulseoximetric oxygen saturations, cardiac output, pulmonary vascularresistance) and controlled removal of the ultrasound catheter can beperformed. The decision on the exact duration of the ultrasound-assistedthrombolysis infusion is at the discretion of the physician, but in oneembodiment it is recommended to continue the treatment for 15 hours (oruntil 20 mg of rt-PA has been delivered) if well tolerated by thepatient.

In certain embodiments, it can be beneficial to keep the cathetercentered in the pulmonary artery during the treatment process. Forexample, centering the ultrasound radiating member 40 in the pulmonaryartery may improve the uniform exposure at the treatment site. In someembodiments, the ultrasound catheter 10 also includes a centeringmechanism for keeping the catheter centered during the treatment. Insome embodiments, the centering mechanism of the catheter 10 can beprovided with one or more balloons disposed around the catheter 10toward the distal region 15.

As described above, in some embodiments, the ultrasound assembly 42comprises a plurality of ultrasound radiating members 40 that aredivided into one or more groups. For example, FIGS. 5 and 6 areschematic wiring diagrams illustrating one technique for connecting fivegroups of ultrasound, radiating members 40 to form the ultrasoundassembly 42. As illustrated in FIG. 5, the ultrasound assembly 42comprises five groups G1, G2, G3, G4, and G5 of ultrasound radiatingmembers 40 that are electrically connected to each other. The fivegroups are also electrically connected to the control system 100. Insome embodiments, two, three, or four or more than five groups ofultrasound radiating member 40 may be electrically connected to eachother and the control system 100. Each group (G1-G5) may comprise one ormore individual ultrasound elements. For example, in one embodiment,each group comprises five or less (i.e., one, two, three, four, or five)ultrasound radiating members 40. In other embodiments, more than 5ultrasound elements can be provided, in each group. Modified embodimentsmay also include different numbers of elements within each group.

In the embodiment of FIG. 6, each group G1-G5 comprises a plurality ofultrasound radiating members 40. Each of the ultrasound radiatingmembers 40 is electrically connected to the common wire 108 and to thelead wire 110 via one of two positive contact wires 112. Thus, whenwired as illustrated, a constant voltage difference will be applied toeach ultrasound radiating member 40 in the group. Although the groupillustrated in FIG. 6 comprises twelve ultrasound radiating members 40,one of ordinary skill in, the art will recognize that more or fewerultrasound radiating members 40 can be included in the group. Likewise,more or fewer than five groups can be included within the ultrasoundassembly 42 illustrated in FIG. 5.

The wiring arrangement described above can be modified to allow eachgroup G1, G2, G3, G4, G5 to be independently powered. Specifically, byproviding a separate power source within the control system 100 for eachgroup, each group can be individually turned on or off, or can be drivenwith an individualized power. This provides the advantage of allowingthe delivery of ultrasonic energy to be “turned off” in regions of thetreatment site where treatment is complete, thus preventing deleteriousor unnecessary ultrasonic energy to be applied to the patient.

The embodiments described above, and illustrated in FIGS. 5 through 7,illustrate a plurality of ultrasound radiating members groupedspatially. That is, in such embodiments, all of the ultrasound radiatingmembers within a certain group are positioned adjacent to each other,such that when a single group is activated, ultrasonic energy isdelivered at a specific length of the ultrasound assembly. However, inmodified embodiments, the ultrasound radiating members of a certaingroup can be interdigitated with respect to ultrasound radiating membersof a different group.

Method for Assembling a Catheter with a Temperature Sensor

As discussed above, the configuration of the temperature sensor 20 inthe exterior tubular body 12 can provide for ease of assembly andmanufacturability. In one aspect, the disclosure resides in a method ofmanufacturing a catheter comprising a flexible circuit and/or a ribbonthermocouple according to any of the embodiments described herein. In aparticular embodiment of the disclosure, the flexible circuit isconfigured to form a thermocouple. In a particular embodiment of thedisclosure, the thermocouple ribbon is configured to form athermocouple. FIG. 13 illustrates a flow-chart of an example method forassembling a catheter with a flex circuit thermocouple and/orthermocouple ribbon.

The method for assembling a catheter with flex circuit thermocoupleand/or thermocouple ribbon can first include block 410 which describesfirst inserting the interior tubular body 13 into the exterior tubularbody 12. In some embodiments, the interior tubular body 13 can beinserted into the exterior tubular body 12 such that the outside surfaceof the interior tubular body 13 contacts the inside surface of theexterior tubular body 12. This can form an asymmetrical space within theexterior tubular body 12 to accommodate a temperature sensor 20.

Next, the method can include block 420 which describes inserting theflexcircuit temperature sensor 20 or and/or thermocouple ribbon 500, 600through the first barb inlet 69 of the distal hub 65. As describedabove, the temperature sensor 20 can be the flexcircuit 220 of FIGS. 2Aand 2B or flexcircuit 320 of FIGS. 12A-12B or ribbon thermocouple 500,660 of FIGS. 2D-2I.

Once inserted, the temperature sensor 20 can be attached to the proximaland distal ends of the interior tubular body 13 as discussed in block430 and block 440. The attachment of the temperature sensor 20 to theinterior tubular body 13 can be done using an adhesive or a heat shrink.

At block 450, the remaining components of the catheter 10 are assembled.For example, in the catheter 10 described above, FIG. 1E illustrates anexploded view of the various components of the catheter 10 and theconnections between each of the components.

Once the catheter 10 has been assembled, the method can include block460 which describes attaching the fluid lines (e.g. fluid line 91 andcooling fluid line 92) to the catheter. As shown above, the fluid line91 can be attached to the second barb inlet 75 while the cooling fluidline 92 is attached to the barb inlet 63.

To attach the temperature sensor 20 to an electrical source, block 470describes connecting the temperature sensor 20 to a cable assembly. Asillustrated in FIG. 1E, the cable 45 can attach to the temperaturesensor 20 through first barb inlet 69. The distal end of the cable 45can then attach to a control system 100. The various methods andtechniques described above provide a number of ways to carry out thedisclosure. Of course, it is to be understood that not necessarily allobjectives or advantages described may be achieved in accordance withany particular embodiment described herein. Thus, for example, thoseskilled in the art will recognize that the methods may be performed in amanner that achieves or optimizes one advantage or group of advantagesas taught herein without necessarily achieving other objectives oradvantages as may be taught or suggested herein.

The disclosure includes the following additional embodiments:

-   -   Embodiment 1. An ultrasound catheter comprising:        -   a first tubular body having a first longitudinal axis            extending centrally through the tubular body, the first            tubular body including at least one delivery port extending            through a wall of the first tubular body;        -   a second tubular body having a second longitudinal axis            extending centrally through the second tubular body, the            first and second, longitudinal axes being displaced from            each other such that an asymmetrical longitudinally            extending gap is formed between an outer surface of the            second tubular body and an interior surface of the first            tubular body;        -   a flexible circuit forming a thermocouple extending            longitudinally within the gap between the first tubular body            and the second tubular body; and        -   an inner core positioned within the second tubular body, the            inner core comprising at least one ultrasound element.    -   Embodiment 2: The ultrasound catheter of Embodiment 1, wherein        the flexible circuit positioned in the widest portion of the        asymmetrical gap.    -   Embodiment 3: The ultrasound catheter of any one of Embodiments        1-2, wherein the flexible circuit extends along the length of        the first tubular body.    -   Embodiment 4: The ultrasound catheter of any one of Embodiments        1-3, wherein the flexible circuit is adjacent to an outer        surface of the second tubular body.    -   Embodiment 5: The ultrasound catheter of any one of Embodiments        1-4, wherein the ultrasound catheter comprises a first fluid        injection port in fluid communication with the gap.    -   Embodiment 6: The ultrasound, catheter of any one of Embodiments        1-5, wherein the apparatus further comprises a second fluid        injection port in fluid communication with an interior of the        second tubular body.    -   Embodiment 7: The ultrasound catheter of any one of Embodiments        1-6, wherein the flexible circuit is configured to measure        temperature at different points along the length of ultrasound        catheter.    -   Embodiment 8: The ultrasound catheter of any one of Embodiments        1-7, wherein the inner core comprises a plurality of ultrasound        radiating members extending along a length of the ultrasound        catheter.    -   Embodiment 9: The ultrasound catheter of Embodiment 8, wherein        the flexible circuit comprises a plurality of joints between        traces of dissimilar materials.    -   Embodiment 10: The ultrasound catheter of Embodiment 9, wherein        the plurality of joints between traces of dissimilar materials        extend along the length of the ultrasound catheter in which the        plurality of ultrasound radiating members is positioned.    -   Embodiment 11: The ultrasound catheter of Embodiment 10, wherein        the joints between traces of dissimilar materials are formed by        a plurality traces of a first material connected to a single        trace of second dissimilar material.    -   Embodiment 12: The ultrasound catheter of Embodiment 1, wherein        the flexible circuit comprises a plurality of traces formed on        the flexible circuit separated by insulating material, the        plurality of traces comprising at least two traces of a first        material connected to a single trace of second dissimilar        material at different points along a length of the flexible        circuit.    -   Embodiment 13: A method of manufacturing a catheter comprising:        -   inserting an inner tubular body into an outer tubular body;            and        -   placing a flexible circuit between the outer and inner            tubular body, wherein the temperature sensor is adjacent to            an outer surface of the inner tubular body such that the            inner tubular body does not extend along the same            longitudinal axis a the outer tubular body.    -   Embodiment 14: The method of manufacturing of Embodiment 13,        wherein the flexible circuit is configured to form a        thermocouple.    -   Embodiment 15: The method of manufacturing of Embodiment 13,        further comprising: forming an inner core, wherein the inner        core is configured to be insertable into the inner tubular body.    -   Embodiment 16: The method of manufacturing of Embodiment 13,        wherein inserting the elongate fluid delivery body and inserting        the temperature sensor forms an asymmetrical cross-section in        the catheter.    -   Embodiment 17: An ultrasound catheter comprising:        -   an elongate inner tubular body;        -   an, elongate outer tubular;            -   wherein the elongate inner tubular body is positioned                within the elongate outer tubular body to form an                asymmetrical gap between an outer surface of the inner                tubular body and an interior surface of the elongate                outer tubular body to form a fluid delivery lumen, and        -   a temperature sensor extending along the outer surface of            the inner tubular body within the gap; and        -   an inner core positioned within the inner tubular body and            comprising at least one ultrasound element.    -   Embodiment 18: The ultrasound catheter of Embodiment 17, wherein        the temperature sensor is formed by a flexible circuit.    -   Embodiment 19: An ultrasound catheter of Embodiment 18, wherein        the temperature sensor is located in the widest portion of the        asymmetrical gap.    -   Embodiment 20: A flexible circuit for a catheter, the flex,        circuit comprising a plurality of traces formed on the flexible        circuit separated by insulating material, the plurality of        traces comprising at least two traces of a first material        connected to a single trace of second dissimilar material at        different points along a length of the flexible circuit.    -   Embodiment 22: The flexible circuit of Embodiment 20, wherein        the second dissimilar material is Constantan and the first        material is copper.

Furthermore, the skilled artisan will recognize the interchangeabilityof various features from different embodiments disclosed herein.Similarly, the various features and steps discussed above, as well asother known equivalents for each such feature or step, can be mixed andmatched by one of ordinary skill in this art to perform methods inaccordance with principles described herein. Additionally, the methodswhich is described and illustrated herein is not limited to the exactsequence of acts described, nor is it necessarily limited to thepractice of all of the acts set forth. Other sequences of events oracts, or less than all of the events, or simultaneous occurrence of theevents, may be utilized in practicing the embodiments of the invention.

Although the invention has been disclosed in the context of certainembodiments and examples, it will be understood by those skilled in theart that the invention extends beyond the specifically disclosedembodiments to other alternative embodiments and/or uses and obviousmodifications and equivalents thereof. Accordingly, the invention is notintended to be limited by the specific disclosures of embodimentsherein.

What is claimed is:
 1. An ultrasound catheter comprising: a firsttubular body having a first longitudinal axis extending centrallythrough the tubular body, the first tubular body including at least onedelivery port extending through a wall of the first tubular body; asecond tubular body having a second longitudinal axis extendingcentrally through the second tubular body, the first and secondlongitudinal axes being displaced from each other such that anasymmetrical longitudinally extending gap is formed between an outersurface of the second tubular body and an interior surface of the firsttubular body; a temperature sensor forming a thermocouple extendinglongitudinally within the gap between the first tubular body and thesecond tubular body; and an inner core positioned within the secondtubular body, the inner core comprising at least one ultrasound element,and the inner core having a third longitudinal axis extending centrallythrough the inner core, wherein the third longitudinal axis is displacedfrom the first and second longitudinal axes.
 2. The ultrasound catheterof claim 1, wherein the temperature sensor is positioned in a widestportion of the asymmetrical gap.
 3. The ultrasound catheter of claim 1,wherein the temperature sensor extends along a length of the firsttubular body.
 4. The ultrasound catheter of claim 1, wherein thetemperature sensor is adjacent to the outer surface of the secondtubular body.
 5. The ultrasound catheter of claim 1, wherein theultrasound catheter comprises a first fluid injection port in fluidcommunication with the gap.
 6. The ultrasound catheter of claim 5,wherein the ultrasound catheter further comprises a second fluidinjection port in fluid communication with an interior of the secondtubular body.
 7. The ultrasound catheter of claims 1, wherein thetemperature sensor is configured to measure temperature at differentpoints along a length of the ultrasound catheter.
 8. The ultrasoundcatheter of claim 1, wherein the inner core comprises a plurality ofultrasound radiating members extending along a length of the ultrasoundcatheter.
 9. The ultrasound catheter of claim 8, wherein the temperaturesensor comprises a flexible circuit that comprises a plurality of jointsbetween traces of dissimilar materials.
 10. The ultrasound catheter ofclaim 9, wherein the plurality of joints between traces of dissimilarmaterials extend along the length of the ultrasound catheter in whichthe plurality of ultrasound radiating members is positioned.
 11. Theultrasound catheter of claim 10, wherein the plurality of joints betweentraces of dissimilar materials are formed by a plurality of traces of afirst material connected to a single trace of second dissimilarmaterial.
 12. The ultrasound catheter of claim 1, wherein thetemperature sensor comprises a plurality of traces formed on thetemperature sensor separated by insulating material, the plurality oftraces comprising at least two traces of a first material connected to asingle trace of second dissimilar material at different points along alength of the temperature sensor.
 13. The ultrasound catheter of claim1, wherein the second tubular body is asymmetrical and includes aplurality of indentations along an interior surface of the secondtubular body.
 14. The ultrasound catheter of claim 1, wherein thetemperature sensor comprises a flexcircuit.
 15. The ultrasound catheterof claim 1, wherein the temperature sensor comprises a plurality offilament pairs wherein each of the plurality of filament pairs isinsulated; and at least one additional thermocouple wherein each of atleast one additional thermocouple are formed between each of theplurality of filament pairs.